ContentslistsavailableatScienceDirect
Industrial
Crops
and
Products
j ourna l h o m e pa g e : w w w . e l s e v i e r . c o m / l o c a t e / i n d c r o p
Review
Asteraceae
species
with
most
prominent
bioactivity
and
their
potential
applications:
A
review
Sílvia
M.F.
Bessada,
João
C.M.
Barreira
∗,
M.Beatriz
P.P.
Oliveira
REQUIMTE,DepartamentodeCiênciasQuímicas,FaculdadedeFarmácia,UniversidadedoPorto,RuaJorgeViterboFerreira,no228,4050-313,Portugal
a
r
t
i
c
l
e
i
n
f
o
Articlehistory: Received28April2015
Receivedinrevisedform24July2015 Accepted28July2015
Availableonline7August2015 Keywords:
Antioxidantandtherapeuticactivity Bioactivecompounds
Food
Medicinalandpharmaceuticaluses Secondarymetabolites
a
b
s
t
r
a
c
t
Oxidativestresshasarelevantpartintheetiologyofseveraldiseasesandmetabolicdisorders,being reasonabletoexpectthatantioxidantcompoundsmighthavebeneficialeffectsinhealthmaintenance ordiseaseprevention.Antioxidantcompoundsmightbeisolatedandcharacterizedfromdifferentplant constituents,suchasroots,stems,bark,leaves,flowers,fruitsandseeds,usingproperextractionmethods. TheAsteraceaefamilyhasaworldwidedistribution,withspecialrelevanceintheMediterranean,Eastern EuropeandAsiaMinor,beingacknowledgedabout25000speciesintegratedinapproximately1000 genera.Inadditiontotheanti-inflammatory,analgesicandantipyreticpotentialofsomeofthesespecies, theirhighantioxidantpower,asproveninresearchworkswithextracts(ofroots,stems,bark,leaves, flowers,fruitsandseeds)shouldbehighlighted.Herein,theAsteraceaespecieswithhighestpotentialas sourcesofnaturalantioxidantswithpotentialusesinmedicineandinpharmaceutical,cosmeticandfood industrieswereidentified.Thespecieswereselectedbasedontheirbotanicalrepresentativeness,being identifiedthe9mostrelevantspecies:AchilleamillefoliumL.,AcmellaoleraceaeMurr.,Artemisiaabsinthium L.,BidenspilosaL.,CarthamustinctoriusL.,InulacrithmoidesL.,MatricariarecutitaL.,OtanthusmaritimusL. andPartheniumhysterophorusL..Withtheobtainedinformation,itcouldbeconcludedthatthebioactivity oftheselectedAsteraceaespecieslacksacompletecharacterization,constitutingaresearchscopewith greatpotentialtobeexploitedinthedevelopmentofdietarysupplements,bioactivefoodingredientsor pharmaceuticalbasedproductswithapplicationinfoodindustry,dermocosmeticsormedicine.
©2015ElsevierB.V.Allrightsreserved.
Contents
1. Introduction...605
2. Reviewmethodology...605
3. Anoverviewoftheassaymethodsusedtoestimateantioxidantcontent...605
3.1. Scavengingcapacityassaysagainststable,non-biological,freeradicals...606
3.1.1. DPPH•method...606
3.1.2. ABTSmethod...606
3.1.3. ScavengingcapacityassaysagainstspecificROS/RNS...606
3.1.4. Superoxideradicalanionscavengingcapacityassays...606
3.1.5. Hydroxylradicalscavengingactivity...606
Abbreviations:AAPH,2,2’,-azobis(2-methylpropionamidine)dihydrochloride;ABTS,[2,2’-azinobis(3-ethylbenzthiazoline-6-sulphonicacid)];AUC,area-under-the-curve; BHA,butylatedhydroxyanisole;CUPRAC,cupricionreducingantioxidantcapacity;DPPH,•2,2-diphenyl-1-picrylhydrazyl;EC50,half-maximaleffectiveconcentration;EDTA, ethylenediaminetetraacetic;ESR,electronspinresonance;FA,fattyacids;FCR,folin-ciocalteureagent;FeIII-TPTZ,ferrictripyridyltriazinecomplex;FRAP,ferricreducing antioxidantpower;H2O2,hydrogenperoxide;HO•,hydroxylradical;HO2•,hydroperoxylradical;HOCl,hypochlorousacid;IC50,50%radicalinhibitionconcentration; MDA,malondialdehyde;NO,nitricoxide;NO•,nitricoxideradical;•NO2,nitrogendioxide;N2O3,dinitrogentrioxide;1O
2,oxygensinglet;O2,•superoxideanion;ONOO−, peroxynitrite;ONOOH,peroxynitrousacid;ORAC,oxygenradicalabsorbancecapacity;PUFA,polyunsaturatedfattyacids;RNS,reactivenitrogenspecies;ROS,reactive oxygenspecies;RP,reducingpower;RSS,reactivesulfurspecies;TAC,totalantioxidantcapacity;TBA,thiobarbituricacid;TBARS,thiobarbituricacidreactivesubstances; TPTZ,2,4,6-tri-(2-pyridyl)-1,3,5-triazine;TRAP,totalradicaltrappingantioxidantparameter.
∗ Correspondingauthorat:CIMO-ESA,InstitutoPolitécnicodeBraganc¸a,CampusdeSantaApolónia,Apartado1172,5301-855Braganc¸a,Portugal.Fax:+351273325405. E-mailaddress:jbarreira@ipb.pt(J.C.M.Barreira).
http://dx.doi.org/10.1016/j.indcrop.2015.07.073
3.1.6. Hydrogenperoxidescavengingassay ... 607
3.1.7. Nitricoxidescavengingactivity...607
3.1.8. Peroxynitritescavengingcapacityassays...607
3.2. Capacityofantioxidantstoreducemetalions(FRAPandCUPRACassays)...607
3.3. Peroxidationinhibitionassays...607
3.3.1. -Carotenediscolorationassay...608
3.3.2. Thiobarbituricacidreactivesubstances(TBARS)assay...608
3.3.3. Hemolysisinhibitionassay...608
3.4. Competitivemethods(ORACandTRAPassays)...608
3.5. Determinationoftotalphenolicandtotalflavonoidcontent...608
3.6. Comparisonamongdifferentantioxidantactivityevaluationmethods...609
4. AntioxidantpotentialofAsteraceaespecieswithbotanicalrelevance...609
4.1. AchilleamillefoliumL...611
4.2. AcmellaoleraceaeMurr...611
4.3. ArtemisiaabsinthiumL...611 4.4. BidenspilosaL. ... 611 4.5. CarthamustinctoriusL...612 4.6. InulacrithmoïdesL...612 4.7. MatricariarecutitaL...612 4.8. OtanthusmaritimusL...612 4.9. PartheniumhysterophorusL...612 5. Conclusion...613 Acknowledgments...613 References...613 1. Introduction
Inrecent research,thecentralroleof oxidativestressinthe developmentofdifferentpathophysiologicalconditionshasbeen widelydiscussed(Flora,2009;López-AlarcónandDenicola,2013). Under stress, the human body produces more reactive oxygen andnitrogenspecies(ROS/RNS)thanenzymaticantioxidantsand non-enzymaticantioxidants,whichmightleadtocelldamageand severalhealthproblems(CarochoandFerreira,2013;Krishnaiah etal.,2011).Thisphysiologicalimbalance(oxidativestress)isakey factorintheonsetofseveralpathologieslikeneurodegenerative (e.g.,Alzheimer’sdisease)andcardiovasculardiseases, inflamma-torydiseases,somecancersandevenaging(Dasarietal.,2013; Jayasenaetal.,2013;Ravishankaretal.,2013).
Infact,oxidativestressisahighlycomplexprocessandits phys-iologicalimpactdependsondifferentfactors,suchasthetypeof oxidantagent,thelocationandintensityofitsproduction,the com-positionandrolesantioxidantcompounds,ortheeffectivenessof repairsystems(Duraˇcková,ˇ 2010).Underdeterminedpathological conditions, the endogenous antioxidant defenses are not suffi-cienttobalancetheincreasedlevelsofcellularoxidativespecies (Benfeitoetal.,2013).Accordingly,theadministrationof exoge-nousantioxidantsmight improve of oxidative status, due their doubleactivityincompensatingtheinefficacyoftheendogenous defensesystemsandintheenhancementoftheoverallantioxidant response(Bergeret al.,2012;Bouayedand Bohn,2010).Hence, antioxidantsmaypreventdifferentoxidative damagepathways, yieldingausefultherapeuticeffect.Thereby,exogenous antioxi-dantsuptakefromdietwillhaveessentialfunctionsinredoxcell homeostasis,modulatingcellfunctionsandactinginthe preven-tionofassociateddiseases(Baghetal.,2011).Hence,adietrichin antioxidantscompounds,naturallypresentinplantsources,would bebeneficialtohumanhealth.Inthiscontext,naturalantioxidants representamajorfieldofresearch,eitherintheoptimizationof experimentaltechniques,asintheiridentificationand characteri-zation(Krishnaiahetal.,2011;López-AlarcónandDenicola,2013). The Asteraceae family includes a highnumber of flowering plants, groupedin nearly 1600 generathat gather over 23,000 species.Someofthesespecies,suchaschamomile(Matricaria recu-titaL.),yarrow(Achilleamillefolium L.),orwormwood(Artemisia
absinthiumL.),arehighlyaromaticandwerepreviouslyreported ashavingmedicinalapplications(Cabraletal.,2013;Kennyetal., 2014).
Thepurposeofthisreviewissurveyingtheantioxidant capac-ity from diverse species of the Asteraceae family, as evidence of theirinterestand applicability assources ofnatural antioxi-dantswithpotentialmedicineand pharmaceuticalapplications, ortobeusedincosmeticandfoodindustries.Thus,attentionhas beendedicated totheantioxidant capacityof natural products, emphasizing those frequentlyor potentially consumed by peo-ple,aswellastheirbotanicalrepresentativenessinthePortuguese territory.
2. Reviewmethodology
Relevantliteraturewascollectedbyscreeningthemajor sci-entificdatabases,includingSciFinder,Sciencedirect,Medlineand GoogleScholar.Sincethesedatabasesareupdatedroutinely,we areawarethatthereviseddataisjustindicativeoftheinformation availableduringthepreparationofthispaper.Amongthescreened publications,relevantreferenceswereselectedconsidering(i)the reportedinvitroandinvivobioactivityevaluationassaysand struc-turalelucidationofbioactivecompoundsisolatedfromthisfamily; (ii)speciesidentificationandinformationregardingthecollection conditions.
3. Anoverviewoftheassaymethodsusedtoestimate antioxidantcontent
Theadvantageousroleofantioxidantsagainstseveraldisorders anddiseasesderived fromoxidativestresshasbeenextensively studied, particularly their functionsin the defense network in vivo. Phenolic compounds (e.g.,phenolic acidsand flavonoids), forinstance,presentanti-inflammatory,anti-carcinogenic,or anti-atheroscleroticactivities(amongotherbiologicaleffects),asresult oftheirantioxidantactivity(Krishnaiahetal.,2011;Niki,2010).
Theevaluationofantioxidantactivityandtheidentificationof specificantioxidantcompoundscanbeperformedthrough differ-entassaysdesignedforspecifictargetswithinthematrix.However, thereisnotabestuniversalmethodbywhichantioxidantcapacity
canbeassessedaccurately,providingunequivocalresults.Infact, severalmethodsweredevelopedandappliedindifferentsystems, but sometimes the produced results are inconsistent, advising theutilizationofvariousmethodsinsteadofasingledimension approach(CarochoandFerreira,2013;Niki,2010).
Someofthemethodsusedtoinvestigatetheantioxidant prop-ertyofsamples(diets,plantextracts,commercialantioxidantsetc.) arebasedonsyntheticantioxidantsorfreeradicals,whileothers needanimalorplantcells.Thesemethodsmighthaveabroadscope ofapplicationorbeingspecificallydesignedtoevaluateaparticular target,suchasinthecaseoflipidperoxidationinhibition evalua-tion.Therequiredknowledgeandtechnicalskillsalsodifferamong methods.Basically,theseassaysdifferfromeachotherintermsof reagents,substrates,experimentalconditions,reactionmediaand analyticalevaluationmethods(Alametal.,2013;Panda,2012).
Consideringthemostrecent studies(Alametal.,2013; Niki,
2010;Panda,2012), themostcommonlyinvitromethods used
forthedeterminationofantioxidantcapacity arereviewed.The assaysarebasedondifferentmechanisms,aimingtoevaluate:(i) thedepletionoffreeradicalsbyantioxidants:scavenging capac-ityassays againststable,non-biological, free radicalsor against specificreactiveoxygenspecies (ROS)/reactive nitrogen species (RNS);(ii)thecapacityofantioxidantstoreducemetalions:ferric reducingantioxidantpower(FRAP)andcupricionreducing antiox-idantcapacity(CUPRAC);(iii)competitivemethods:oxygenradical absorbancecapacity(ORAC)andtotalradicaltrappingantioxidant parameter(TRAP);(iv)determinationoftotalphenolicandtotal flavonoidcontent;(v)reducingpower(RP).
3.1. Scavengingcapacityassaysagainststable,non-biological, freeradicals
Among free radical scavenging methods, 2,2-diphenyl-1-picrylhydrazyl (DPPH•)method is more rapid, simple (i.e., not involvedwithmanystepsandreagents)andinexpensivein com-parisontoothertestmodels.Ontheotherhand,2,2 -azinobis(3-ethylbenzthiazoline-6-sulphonicacid)(ABTS)decolorizingassayis applicableforbothhydrophilicandlipophilicantioxidants(Alam etal.,2013;Panda,2012).
3.1.1. DPPH•method
DPPH•isbasedontheprinciplethatahydrogendonormightbe consideredasanantioxidant.Thiswidelyusedcolorimetricassay usestheDPPH•stablefreeradical,whichhasastrongpurplecolor thatchangestoyellow(reducedform)inthepresenceof antioxi-dants.DPPH•issolubleinorganicsolventsandpresentsatypical absorptionbandat515nm.Theantioxidantactivityismeasured bythedecreaseinabsorptionat515–528nm,whichresultsfrom beingreducedbytheantioxidantinsolution.Theprotocolsusedto applythismethoddifferintheconcentrationofDPPH•,incubation time,reactionsolventandpHofthereactionmixture.Ingeneral, thereactionmixtureshouldbepreparedusingaratioof5loftest sampleand95lofDPPH• (300M)inmethanol(Chetanetal., 2012).ThereactionforscavengingDPPH• radicalisusually car-riedoutat37◦Cindarkfor30minandtheabsorbanceisrecorded at517nm.Alargedecreaseintheabsorbanceattheendpointof thereactionindicatesstrongfreeradicalscavengingactivityofthe testedcompound/extract(Alametal.,2013;Krishnaiahetal.,2011; MoonandShibamoto,2009;SharmaandBhat,2009).
3.1.2. ABTSmethod
TheABTSassayisacolorimetricassayinwhichtheABTS radi-calsuffersacolordecreaseinthepresenceofantioxidants.Usually theABTScationradical(ABTS•+)ispreparedinsolutionwith potas-sium,andthemixtureisfurtherincubatedatroomtemperaturein thedarkfor12h.TheABTS•+isgeneratedbytheoxidationofABTS
withpotassiumpersulfate,anditsreductionbyhydrogen-donating antioxidantsismeasuredspectrophotometricallyat734nm.The resultingsolutionisoftendilutedwithmethanoltogetan appro-priate absorbance. Due to the solubility of ABTS•+ in aqueous andorganicsolvents,this decolorizingassaymeasuresthetotal antioxidantcapacityinlipophilicand hydrophilicsubstances.In the determination of the antioxidant activity, theeffect of the antioxidantconcentrationandtheperiodtakentoinhibitthe rad-icalcation’sabsorptionshouldbeconsidered(Chetanetal.,2012; Krishnaiahetal.,2011;MoonandShibamoto,2009;Niki,2010).
3.1.3. ScavengingcapacityassaysagainstspecificROS/RNS
Freeradicalsareatoms,moleculesorionswithunpaired elec-trons,whicharehighlyactiveinchemicalreactions.Inbiological systems,thefreeradicalsareoftenderivedfromoxygen,nitrogen andsulfurmolecules(Fig.1).Thesefreeradicalsintegrategroups ofmoleculescalledROS,RNSandreactivesulfurspecies(RSS).ROS, forinstance,includefreeradicalssuchassuperoxideanion(O2−•), hydroperoxyl radical(HO2),hydroxyl radical(HO•), nitricoxide (NO),andotherspeciessuchashydrogenperoxide(H2O2),oxygen singlet(1O
2)andhypochlorousacid(HOCl)(CarochoandFerreira, 2013).RNSareproducedinanimals,derivedfromthereactionofNO withO2−•toformperoxynitrite(ONOO−).Additionally,ONOO−can reactwithothermoleculestoformadditionaltypesofRNS includ-ingnitrogendioxide•NO2)anddinitrogentrioxide(N2O3)(Pacher etal.,2007).RSS,ontheotherside,areproducedfromthiolstoform adisulfidethatmightbefurtheroxidizedtodisulfide-S-monoxide ordisulfide-S-dioxide.Theseintermediatemoleculescanreactwith areducedthiolproducingsulfenicorsulfinicacid(Gilesetal.,2001).
3.1.4. Superoxideradicalanionscavengingcapacityassays
Althoughsuperoxideanion isaweakoxidant,it isthe start-ingpointfortheproductionofpowerfulanddangeroushydroxyl radicalsandsingletoxygen,bothcontributingtooxidativestress. Thesuperoxideanionscavengingactivitycanbemeasuredafter itsgenerationinTris–HClbuffer,containingnitrobluetetrazolium (NBT),0.5mlNADHsolutionandthetargetsample.Thereaction isinitiatedthroughtheadditionofphenazinemethosulfate(PMS) solution,andfurtherincubationat25◦Cfor5minfollowedby mea-suringtheabsorbanceat560nm(Magalhãesetal.,2008;Meyerand Isaksen,1995;RobakandGryglewski,1988).
3.1.5. Hydroxylradicalscavengingactivity
Hydroxylradical(HO•)isoneofthemostpotentROSspecies inbiologicalsystems,beingparticularlyactiveagainstthe polyun-saturated fatty acidmoieties of cell membrane phospholipidic layer.Oneof thestandardmethodologies (Kunchandyand Rao, 1990)usedtoevaluatethescavengingabilityofhydroxylradicals consistsofmixingtheextractwith2-deoxy-d-ribose(inKH2PO4 -KOHbuffer),ethylenediaminetetraaceticacid(EDTA),FeCl3,H2O2 and ascorbic acidand furtherincubation (37◦C, 1h).The reac-tioniscontinuedthroughtheadditionofthiobarbituricacidand trichloroaceticacid,andsubsequentlyincubated(100◦C,20min). Aftercooling,absorbanceismeasuredat532nm,againstablank sample.ConsideringthehighreactivityofHO•,almostallchemical speciesinbiologicalsystemscanberegardedasanHO•scavenger. Actually,thisactivityisnotperformedbyanyspecificmoleculeor enzyme,whichmightdiminishtherelevanceofdirectlyevaluating thescavengingofHO•,simplybecauseveryhighconcentrationsof scavengerarerequiredtocompetewithadjacentmoleculesinvivo orinthefoodmatricesforanygeneratedHO•.Hence,itismore usefultoquantifythecapacityofpotentialantioxidantsto scav-engetheformationofitsprecursorsand/ortocapturefreemetal ionsrelatedtoHO•formation.Thescavengercompoundswiththis
2nd line 3rd line 4th line Prooxidant?
Anoxidants
Message signaling Gene expression Adaptaon Free radicals ROS/RNS/RSS Redox imbalance Oxidave stress Oxidation of molecules Oxidave damage Diseases AgingInducon of defense enzymes
1st line
Repair de novo Radical scavenging
Metal chelang
Fig.1.Defensenetworkinvivoagainstoxidativestress.Severalantioxidantsplaydifferentrolesaccordingtothedefenselevelandmodeofaction.AdaptedfromNiki(2010).
typeofbehaviorwouldactaspreventiveantioxidants(Alametal., 2013;Magalhãesetal.,2008).
3.1.6. Hydrogenperoxidescavengingassay
Human beings are indirectly exposed toH2O2 via the envi-ronment(nearly0.28mgkg−1day−1)withintakemostlyfromleaf crops.H2O2 mayenterintothehumanbodythroughinhalation ofvaporormistandthrougheyeorskincontact.It ispromptly decomposedinoxygenandwater,whichmightproduceHO•that caninitiatelipidperoxidationandcauseDNAdamageinthebody. TheabilityofplantextractstoscavengeH2O2isusuallyestimated usingabuffered(phosphatebuffer)solutionofH2O2inmixture withtheextractandsubsequentevaluationoftheabsorbanceat 230nm(Alametal.,2013;Panda,2012;Ruchetal.,1989). 3.1.7. Nitricoxidescavengingactivity
Nitricoxideradical(NO•), acclaimedasthe“moleculeofthe year”in 1992bytheScience Magazine(Koshland,1992), hasa keyroleinthemodulationofdiversephysiological processes.It isknownthatthenitricoxidegeneratedfromsodium nitroprus-sideinaqueoussolutionandphysiologicalpHreactswithoxygen toproducenitriteions,whichcanbequantifiedusingtheGriess reactionreagent,sodiumnitroprusside(phosphatebuffer),the tar-getextract and a referencecompound. Ablank solutionisalso preparedwithmethanoland thesolutions areincubated(25◦C, 60min),andfurtherevaluatedspectrophotometrically(540nm). Theinhibitionofthegeneratednitriteoxideisquantifiedby com-paringtheabsorbancevaluesofcontrolandtestsamples.Curcumin, caffeicacid,sodiumnitrite,butylatedhydroxyanisole(BHA), ascor-bicacidandrutinaretypicallyusedasapositivecontrol(Dasgupta andDe,2007;Magalhãesetal.,2008;Panda,2012).
3.1.8. Peroxynitritescavengingcapacityassays
Peroxynitrite(ONOO−)andperoxynitrousacid(ONOOH)cause nitration or hydroxylation in aromatic compounds, particularly in tyrosine. Under physiologic conditions, peroxynitrite might alsoproduce an adduct with theCO2 dissolved in body fluids. Thisadducthasbeenreportedasinducingdamagesinproteins. Presently,themethods tomeasureONOO−aretheinhibitionof tyrosinenitrationandtheinhibitionofdihydrorhodamine-123 oxi-dation.Theelectron spinresonance(ESR)spectrometryassayis
theonlyprocedureabletodetectspecificfreeradicalsinvolvedin autoxidationprocesses(Antolovichetal.,2002;Huangetal.,2005). 3.2. Capacityofantioxidantstoreducemetalions(FRAPand CUPRACassays)
Thesemethodsevaluatethecapacityofsamplestoreduceferric orcupricionsinaqueousmedia.TheFRAP(ferricreducing antiox-idantpower)assay,originallydevelopedtoevaluatetheabilityof humanplasmaas antioxidant,is basedonthereduction of the ferricironincomplexwith2,4,6-tri-(2-pyridyl)-1,3,5-triazine(Fe III-TPTZ)totheferrousformatlowpH,measuringtheabilityof antioxidantsas ferriciron reducing agents. FRAPvalues can be obtainedbycomparingabsorptionchanges(593nm)inthetest mixturewiththoseobtainedfromincreasingconcentrationsofFe IIIandexpressedasmMofFeIIequivalentskg−1(solidsamples) orl−1(liquidsamples)ofsample(BenzieandStrain,1996,1999; Panda,2012).
CUPRACmethoddeterminesthepotentialofasampletoreduce the neocuproine-cupric complex (Nc–Cu II). In this case, the complexofNcwiththereducedformofthemetalpresentsa char-acteristicabsorptionbandwithmaximalintensityat450nm.Thus, thecapacitytoreducethemetalcomplexes(generatingthe corre-spondingabsorptionbands)alongafixedincubationtimeallows determining FRAP or CUPRACvalues. Nevertheless, while FRAP assayrequiresanacidicpH(3.6),thatisfarfromthephysiological pHvalue,CUPRACassayisperformedatpH7.0,simulatingbetter thephysiologicalconditions.Inaddition,CUPRACassay differen-tiatesthereducingpowerofthiol-typeantioxidants(Apaketal., 2004;Güngöretal.,2011).
3.3. Peroxidationinhibitionassays
Somelipidmolecules,e.g.,polyunsaturatedfattyacids(PUFA), ortheircorrespondingesterifiedforms,andcholesterolare vul-nerabletofreeradicalsattack.Lipidperoxidationinduceschanges in the biological membranes and produces potentially toxic compounds.Asa startingpoint, the␣,-unsaturatedcarbonylic compounds (e.g.,4-hydroxynonenal e acroleine) resulting from lipidicperoxidation,modifyessentialmoleculessuchasproteins andDNA,whichcantriggerimbalancesanddisease.Antioxidants canslowthisprocessinfoodsandbiologicalsystems(Blair,2008).
Therearehighlyspecifictechniquesavailableforthe evalua-tionofoxidationinmembranes,lipidspresentinfood,lipoproteins andfattyacids(FA).Theantioxidanteffectonlipidperoxidation ismeasuredbysubstrateloss,assayswithperoxidesorby deter-miningfinalproducts(Niki,2010).Thelipidsubstratesthatmay beusedincludeemulsionsorliposomesproducedfromFAortheir esterifiedforms.Thebiologicalsystemsmightbeerythrocytesor isolatedlipoproteins(Antolovichetal.,2002).
3.3.1. ˇ-Carotenediscolorationassay
Carotenoids can be suffer discoloration by auto-oxidation inducedbylight,heatorROO•(Karadagetal.,2009).-carotene undergorapiddiscoloration inthepresence ofa linoleate radi-cal.Duringtheoxidation,anHatomisremovedfromtheactive methylenebis-allylgrouplocatedintheC11 positionoflinoleic acid,betweentwodoublebonds.Thenewlyformed cyclopentadi-enylradicalattacks-caroteneunsaturatedmoleculestoreacquire Hatoms.When-carotenemoleculeslosetheirconjugation,the orange color lost might be followed by spectrophotometry at 470nm(Amarowiczetal.,2004;BurdaandOleszek, 2001).The kineticapproachallowsthedeterminationofcompleteinhibition effectsandprovidesamoreaccurateassessmentoftheefficiency ofantioxidantdefenses,althoughthereactivityand antioxidant capacitycannotbedeterminedseparately(Karadagetal.,2009).
Theadditionofasamplecontainingantioxidantcompoundsor plantextractshastheabilitytoinhibitdiscolorationof-carotene (Laguerreetal.,2007).
However,despite -caroteneis oftenused asa target com-pound,thediscolorationmayoccurat470nmbydifferentways, which might difficult the interpretationof results(Prior et al., 2005).
3.3.2. Thiobarbituricacidreactivesubstances(TBARS)assay TBARSassayiswidelyusedforthedetectionoflipidoxidation. Thismethodmeasuresthemalondialdehyde(MDA)formedfrom unsaturatedFAcleavageuponoxidationofalipidsubstrate.The for-mationofMDAfromFAwithlessthanthreedoublebondsoccurs throughthesecondaryoxidationofprimarycarbonylcompounds (Fernándezetal.,1997).MDAreactswiththiobarbituricacid(TBA), formingapinkpigment(TBARS)whichismeasured spectropho-tometricallyat532nm(Ngetal.,2000).Theprocedureinvolves twodistinctsteps:thesubstrateisoxidizedafteradditionof tran-sitionmetal(suchasironorcopper)ion,orafreeradical;thenthe extentoftheoxidationisdefinedbytheadditionofTBAandthe spectrophotometricmeasurementoftheproduct.Theoxidationis inhibitedbytheadditionofanantioxidant,wherebythedecrease inabsorbancecanbemeasured.Resultsaretypicallyquantifiedin termsofoxidationinhibitionpercentage(Antolovichetal.,2002). 3.3.3. Hemolysisinhibitionassay
Theerythrocytesarevulnerabletolipidperoxidationduetoits highcontentofpolyunsaturatedlipids,thelargesupplyofoxygen andthepresenceoftransitionmetals(Zhuetal.,2002).Whenthe erythrocytesaresubjectedtooxidativestress,freeradicals lead toformationofhemolyticporesinthecellmembrane.Thisinjury resultsinapotassiumleakagetotheextracellularenvironmentand consequenthemolysis(Bureauetal.,2005).Sincelipidperoxidation isachainreactionoffreeradicals,andconsideringthatafree radi-calcaninduceuptotwentypropagationreactions,themembrane ofredbloodcellsisreadilydamaged.Inthepresenceofantioxidant compounds,theyreactwiththeROO•chainpropagators,stopping peroxidationandtherebyinhibitinghemolysis(Daietal.,2006).
Theazocompound2,2-azobis(2-methylpropionamidine) dihy-drochloride(AAPH,sometimesalsoabbreviatedasABAP)canbe decomposeatphysiologicaltemperaturetoproducealkylradicals, initiatinglipidperoxidation.OncetheAAPHiswater-solubleand
therateoffreeradicalgenerationcanbecontrolled,ithasbeen extensivelyusedasfreeradicalsinitiatorinbiologicalstudies(Dai etal.,2006;Nikietal.,1988).
Theuseoferythrocytesasamodelsystemshasbeenapplied extensivelytostudyoxidativedamagein biologicalmembranes (Mabileetal.,2001),astheinhibitionofhemolysismaybe spec-trophotometricallymonitoredat540nm(Ngetal.,2000). 3.4. Competitivemethods(ORACandTRAPassays)
Thesemethodologiesevaluatetheabilitytoinhibitthedepletion ofatargetmolecule(usuallymonitoredbyUV-visibleabsorption orfluorescencespectroscopy)mediatedbyperoxylradicals. Usu-ally,AAPHisemployedasperoxylradical(ROO•)source,generating theseradicalsataknownrateinthefirsthoursofincubationin aqueousmedia(López-AlarcónandDenicola,2013).
TheORACassayusesbeta-phycoerythrin(-PE)orfluorescein asanoxidizableproteinsubstrate(targetmolecule)andAAPHas aperoxylradicalgeneratororaCu2+-H
2O2systemasahydroxyl radicalgenerator.Thisassayisbasedinmeasuringthedecreasein fluorescenceinthepresenceoffreeradicalscavengers(Troloxisa commonlyusedstandardcontrol).Todate,itistheonlymethod basedinacompletefreeradicalreactionthatusesan area-under-the-curve(AUC)techniqueforquantification.Thisapproachallows combiningtheinhibitionpercentageandthedurationofinhibition ofthefreeradical’sactionintoasinglequantity.Theassayhasbeen usedinmanyrecentstudiesofplants(Alametal.,2013;Krishnaiah etal.,2011;Panda,2012;Prioretal.,2003).
Inrecentyears,TRAPisthemostwidelyusedinvivomethod formeasuringtotalantioxidantcapacityofplasmaorserum.This methodusesperoxylradicalsgeneratedfromAAPHand peroxidiz-ablematerialspresentinplasmaorotherbiologicalfluids.After addingAAPHtotheplasma,theoxidationismonitoredby mea-suringtheoxygenconsumedduringthereaction.Throughoutan inductionperiod,thisoxidationisinhibitedbytheantioxidantsin theplasma.Inthisassay,therateofperoxidationinducedbyAAPH ismonitoredthroughthedecreaseinthefluorescenceofthe pro-teinR-phycoerythrin(R-PE)(Badarinathetal.,2010;Huangetal., 2005;Niki,2010).
3.5. Determinationoftotalphenolicandtotalflavonoidcontent Theamountof total phenoliccontent canbedeterminedby Folin-Ciocalteureagent(FCR)method.Theexactchemicalnature oftheFCRisnotknown,butitisgenerallyacceptedthatitcontains complexesoffosfomolibdic/fosfotungsticacid.Thechemical reac-tionisbasedontheelectrontransferinalkalineconditionsfrom phenolic compounds and other molybdenum reducing species, originatingbluecomplexesthatmightbemeasured spectropho-tometrically(Magalhãesetal.,2008).Thesamplesolutionismixed withtheFCR (previouslydiluted) and allowedto stand(3min, 25◦C)beforeasaturatedsodiumcarbonatesolutionisadded.The mixedsolutioniskept(120min)inthedarkbeforetheabsorbance ismeasured(725nm).Gallicacidisusedasastandardforthe cali-brationcurveandthetotalphenolicscontentisexpressedasgallic acid equivalents (MacDonald-Wicks et al., 2006; Panda, 2012). Despiteitswideuse,theFCRmethodpresentssomelimitations, suchasthepossibility ofusing differentstandardsbesides gal-licacid,thefactthatthefinalabsorbanceisproportionaltothe number of HO• groups(depending alsoonthemolecule struc-ture)andmainlybecausethereagentmightbereducedbyother compoundsthanphenolics(e.g.,ascorbicacid,reducing sugars). Furthermore,itislimitedtohydrophilicantioxidants.Usually,the identificationandquantificationofphenoliccompoundsshouldbe achievedthroughchromatographictechniquesinassociationwith
Fig.2.Basicchemicalstructuresofcommonclassesofflavonoids.(1)Flavones; (2)flavanones;(3)isoflavones;(4)flavonols;(5)flavanols;(6)flavanonols;(7) isoflavones.
massspectrometryornuclearmagneticresonance(Karadagetal., 2009).
Flavonoids are ubiquitous in plants and contribute to the sensorial qualities of foods (Harborne and Williams, 2000). These phytochemicals are usually classified as dietetic antiox-idants because the HO• groups near -conjugated electron systemspromptlygivehydrogentoROSandRNS(Milburyetal., 2006). Flavonoids are subdivided in different classes such as flavones,flavanones,isoflavones,flavonols,flavanols,flavanonols andisoflavones(Fig.2),withflavan-3-olsandanthocyaninsasthe majorclassesamongplants(RobardsandAntolovich,1997).Their antioxidantactivitydependsontheirchemicalstructure, partic-ularlyontheHO• groupspositioninthemolecule.Besidestheir capacitytodonatehydrogenorelectronstofreeradicals,chelation ofmetalionsandinhibitionofenzymesresponsibleforfree radi-calgeneration,flavonoids(especiallyisoflavones)mightexerttheir effectsviadifferentmechanismssuchasthemodulationof
cellu-larsignalingpathways,mitochondrialinteractionsandchangesin geneticexpression(Hernandez-Montesetal.,2006).
Flavonoidsareoftendeterminedfollowingacolorimetricassay, inwhichthesampleismixedwithareagentcontainingaluminum chloride and sodium nitrite, producing a flavonoid-aluminum complex with a rosaceous color in alkaline medium (Zhishen etal.,1999).Thealuminumcationformsstablecomplexeswith flavonoids,causinga shifttohigherwavelenghts(bathocromic). Phenolic acids, even those forming complexes withaluminium chloride,absorbinmuchlowerwavelelenghts,therebyavoiding interferencesintheobtainedabsorbances.Quercetinorcatechin canbeusedasapositive control.Theflavonoidcontentis usu-allyexpressedintermsofstandardequivalent(mgg−1ofextracted compound)(DenniandMammen,2012;Ordo ˜nezetal.,2006). 3.6. Comparisonamongdifferentantioxidantactivityevaluation methods
Any given antioxidant activity evaluation method should includeanoxidationinitiator,anadequatesubstrateandtheexact definitionofthereactionendpoint.Initiatorsmightbeanincrease intemperatureor inthepartialpressureof oxygen,additionof metalcatalyzers,exposuretolighttopromotephoto-induced oxi-dationorshaking topromotecontact amongreagents(Karadag etal.,2009).Theevaluationoftheantioxidantactivityin biologi-calmatricesininfluencedbydifferentfactorssuchasantioxidants’ partitioncoefficientsamongaqueousandlipidicphases,oxidation conditionsandphysicalstateoftheoxidizablesubstrate(Frankel andMeyer, 2000).Inconclusion,astandard antioxidantactivity evaluationmethodshould:(i)measurethepotentiallyoccurring chemicaltransformations;(ii)useafreeradicalsourcewith biolog-icalrelevance;(iii)achievableusingsimpletechnologicalmethods; (iv)haveawell-knownreactiontimeandmechanism;(v)be attain-ablewithequipmentcommonlyavailableinthelaboratory;(vi) have good reproducibility among assays; (vii) be adaptable to hydrophilicandlipophilicantioxidants;(viii)beapplicableto dif-ferenttypesoffreeradicals(Prioretal.,2005).
4. AntioxidantpotentialofAsteraceaespecieswith botanicalrelevance
Someresearchersproposethattwo-thirdsoftheworld’splant specieshavemedicinalvalue(Krishnaiahetal.,2011).This poten-tialbiologicalactivityis oftenrelatedtotheirgreatantioxidant capacity. Therefore, medicinalplants used in folk medicineare raisingincreasinginterestfortheirpotentialapplicationin phar-maceutical,foodandnutraceuticalfields.Inaddition,thesocalled phytomedicinesareplayingaprogressivelyhigherroleinhuman health care system. Considering the social demands related to healthand nutrition,medicinalplantsemergeasastrong alter-nativetosyntheticproducts,usedbothintraditionalmedicineand infoodandpharmaceuticalproducts,duetotheirnutritional prop-ertiesandbioactivity.Duetotheirhighrangeofapplication,itis usefultoelucidatetheirmechanismsofaction,inordertodevelop bettermedicinalproducts.Plantscontainahighdiversityoffree radicalscavengingmolecules,suchasphenoliccompounds, nitro-gencompounds,vitamins,terpenoids,amongothers(Chetanetal., 2012;Phillipson,2007).
TheAsteraceaefamilyconsistsofapproximately1000genera, whichcompriseover25,000speciesoffloweringplants,somewith wide usesfor medicinalpurposes, asin thecase ofchamomile (M.recutitaL.),yarrow(A.millefoliumL.),orwormwood(Artemisia absinthiumL.).Differenttypesofbiologicalactivitieswere previ-ouslyreportedinseveralAsteraceaespeciesthroughouttheworld (Table1).Despitetherelativelyhighnumberofstudiesreporting
Table1
BioactivityscreeningassaysperformedusingAsteraceaespeciesfromdifferentgeographiclocations.
Species Assays Origin Authors
Achilleabeibersteni Phenolscontent;antioxidantactivity SaudiArabia Shahatetal.(2014)
Achilleafragrantissima Phenolscontent;antioxidantactivity SaudiArabia Shahatetal.(2014)
Achilleamillefolium Anxiolyticactivity Brazil Barettaetal.(2012)
Antimicrobialandantioxidantactivitites Turkey Candanetal.(2003)
Vasoprotectiveactivity Italy Dall’Acquaetal.(2011)
Phytochemicals,antioxidantandantitumoractivities Portugal Diasetal.(2013)
Phenolscontent;antioxidantactivity Iran Gharibietal.(2013)
Antiulcerogenicandantioxidantactivities Brazil Potrichetal.(2010)
Hypotensiveeffects Brazil Souzaetal.(2011)
Phenoliccompounds;antioxidantactivity Italy Vitalinietal.(2011)
Antioxidantactivityandmodulationofmitochondriarespiration Lithuania Trumbeckaiteetal.(2011)
Acmellaoleraceae Phytochemicalsandantioxidantactivity SriLanka Abeysirietal.(2013)
Ageratumconyzoides Analgesicpotential;antioxidantactivity Bangladesh Dewanetal.(2013)
Ageratumhoustonianum Antioxidantactivity India Tennysonetal.(2012)
Ambrosiaartemisiifolia Antioxidantactivity Serbia Maksimovi ´c(2008)
Anthemisdeserti Phenolscontent;antioxidantactivity SaudiArabia Shahatetal.(2014)
Arctiumminus Antimicrobialandantioxidantactivitites Ireland Kennyetal.(2014)
Artemisiaabsinthium Hepatoprotectiveactivity China Amatetal.(2010)
Phytochemicals,antifungalandantiparasiticactivities Spain Bailenetal.(2013)
Neuroprotectiveactivity India BoraandSharma(2010)
Antioxidantactivity Serbia Canadanovic-Brunetetal.(2005)
Antifeedant,antiparasiticandantioxidantactivities Spain Gonzalez-Colomaetal.(2012)
Phenoliccompounds;antioxidantactivity Australia Leeetal.(2013)
Anti-venomactivity Turkey Nalbantsoyetal.(2013)
Antitumoractivity India Shafietal.(2012)
Anthelminticactivity India Tariqetal.(2009)
Artemisiamonosperma Phenolscontent;antioxidantactivity SaudiArabia Shahatetal.(2014)
Bidenspilosa Antioxidantandimmunomodulatoryactivities Cuba Abajoetal.(2004)
Antidiabeticactivity Taiwan Chienetal.(2009)
Antioxidantandantimicrobialactivities Japan Debaetal.(2008)
Anti-hypertensiveactivity Cameroon Dimoetal.(2002)
Anti-hyperglycemicactivity Taiwan Hsuetal.(2009)
Antitumoractivity Brazil Kviecinskietal.(2008)
Immunosuppressiveandanti-inflammatory Brazil Pereiraetal.(1999)
Antimalarialactivity Brazil Oliveiraetal.(2004)
Antioxidantactivity Taiwan Yangetal.(2006)
Carthamustinctorius Severalbiologicalactivities Severalorigins Zhouetal.(2014)
Centaureanigra Antimicrobialandantioxidantactivitites Ireland Kennyetal.(2014)
Centaureapaniculata Phytochemicals;antioxidantactivity Portugal Barrosetal.(2010)
Centaureascabiosa Antimicrobialandantioxidantactivitites Ireland Kennyetal.(2014)
Chicoriumintybus Antioxidantactivity Poland Rozp ˛adeketal.(2014)
Cirsiumarvense Antimicrobialandantioxidantactivitites Ireland Kennyetal.(2014)
Cirsiumpalustre Antimicrobialandantioxidantactivitites Ireland Kennyetal.(2014)
Cirsiumvulgare Antimicrobialandantioxidantactivitites Ireland Kennyetal.(2014)
Echinaceapurpurea Antimicrobial Portugal Martinsetal.(2015)
Eriocephalusspp. Enzymaticinhibition;antioxidantactivity South-Africa NjengaandViljoen(2006)
Helichrysumspp. Antimicrobialandantioxidantactivitites Turkey Albayraketal.(2010)
Helichrysumstoechas Phytochemicals;antioxidantactivity Portugal Barrosetal.(2010)
Inulacrithmoïdes Antioxidant,anticlastogenicandantimutagenicactivities Egypt Abdel-Wahhabetal.(2008)
Antimicrobialandantioxidantactivitites Tunisia Jallalietal.(2014)
Herbicidalactivity Tunisia Omezzineetal.(2011)
Lychnophorapasserina Flavonoidscontent;antioxidantactivity Brazil Chicaroetal.(2004)
Matricariarecutita Phytochemicals;antioxidantactivity Portugal Barrosetal.(2010)
Neuroprotectiveactivity India Chandrashekharetal.(2010)
Anti-allergicactivity India Chandrashekharetal.(2011)
Phytochemicals,antioxidantactivity,cytotoxicity Portugal Guimarãesetal.(2013)
Antimicrobialactivity Iran Jamalianetal.(2012)
Severalbiologicalactivities Severalcountries McKayandBlumberg(2006)
Antioxidantactivity Portugal Martinsetal.(2015)
Antidiarrhealandantioxidantactivities Tunisia Sebaietal.(2014)
Mikaniacordifolia Analgesicpotential;antioxidantactivity Bangladesh Dewanetal.(2013)
Otanthusmaritimus Antimicrobialandcytotoxicityactivies Portugal Cabraletal.(2013)
Repellencyagainsinsects Greece Tsoukatouetal.(2000)
Parthenium hysterophorus
Cytotoxicactivity India Dasetal.(2007)
Antioxidantactivity India Krishnaveni(2013)
Antioxidantactivity India Kumaretal.(2013)
Antibacterial,antioxidant,andcytotoxicactivities India Kumaretal.(2014)
Antifungalactivity India Rajivetal.(2013)
Antioxidantactivity Pakistan UdDinetal.(2015)
Picriscyanocarpa Phenolscontent;antioxidantactivity SaudiArabia Shahatetal.(2014)
Pulicariacrispa Phenolscontent;antioxidantactivity SaudiArabia Shahatetal.(2014)
Rhantariumepapposum Phenolscontent;antioxidantactivity SaudiArabia Shahatetal.(2014)
Sonchusasper Antimicrobialandantioxidantactivitites Ireland Kennyetal.(2014)
Taraxacumofficinale Antimicrobialandantioxidantactivitites Ireland Kennyetal.(2014)
Taraxacumsect.Ruderalia Phenolscontent;antioxidantactivity Portugal Diasetal.(2014)
theirbiologicalpotential,Portuguesespecieswerescarcely inves-tigatedandthespecieswithhighestpotentialwillbetheprimary focusofattentioninthenextsection.Consideringthissubject,the presentreviewisespeciallydedicatedtotheinvitroantioxidant propertiesofextractsfromthestems,roots,bark,leaves,flowers, fruitsandseedsoftheAsteraceaespecieswithbotanicalrelevance inPortugal.
4.1. AchilleamillefoliumL.
A.millefoliumL.,commonlyknownasyarrow(milefólioor erva-carpinteira)iswidespreadinmountainmeadows,pathways,crop fieldsand homegardens. Itsinfusionand alcoholicextractsare widelyusedtotreatdigestiveproblems,diabetes,hepato-biliary diseases and amenorrhea, being also consumed for its antitu-mor,antimicrobial,anti-inflammatoryandantioxidantproperties, amongothers.Whenconsumedin theformofadecoction,itis mainlyusedfordigestiveandintestinaldisorders,besidesbeing externallyusedforskinandmucosainflammations(Barettaetal., 2012;Gharibietal.,2013;Potrichetal.,2010).
Inarecentscientificstudy(Diasetal.,2013),wildand commer-cialsamplesofA.millefoliumL.werechemicallycharacterizedfor theirmacronutrients,sugars,organicacids,FAandtocopherols.In addition,theinvitroantioxidantproperties(freeradicals scaveng-ingactivity,reducingpowerandlipidperoxidationinhibition)and theantitumorpotential(againstbreast,lung,cervicaland hepato-cellularcarcinomacelllines)oftheirmethanolicextracts,infusions anddecoctionswereevaluatedandcorrelatedtothecorresponding phenolicprofiles.Ingeneral,commercialyarrowpresentedlower EC50(half-maximaleffectiveconcentration)values(higher antiox-idantactivity). Concerning theextract type,decoctions showed thehighest DPPH• scavengingactivity (0.25±0.01mgml−1), -carotene bleaching inhibition (0.18±0.03mg.ml−1) and TBARS inhibition (0.04±0.01mgml−1), while infusions presented the highestreducingpower(0.12±0.01mgml−1)(Diasetal.,2013).
ThemajorantioxidantcompoundsfoundinA.millefoliumare flavonoidslikeapigeninand quercetin,andphenolic acids (e.g., caffeoylquinicacid),whichareknowntoactasreducingagents, hydrogendonatorsorsingletoxygenquenchers againstreactive speciesinvolvedinoxidativestress.ThephytochemicalprofileofA. millefoliumshowedalsorelevantcontentsinorganicacids(mainly oxalic,quinic,andcitric),FA(withlinoleicandpalmiticacidsas themajorones)andtocopherols(specially,␥-tocopherol)(Benedek etal.,2007;Diasetal.,2013;Gharibietal.,2013;Vitalinietal., 2011).
4.2. AcmellaoleraceaeMurr.
A.oleraceaeMurr.(alsoknownasSpilanthesacmella)isa ther-apeuticallyimportantannualor short-livedperennialmedicinal herbwithyellow, non-fragrantflowers(Abeysirietal.,2013).It hasbeenwidelyusedinAyurvedaandfolksystemsofmedicineas ananti-inflammatory,antisepticandanestheticdrugsincehistoric times.Intraditionalmedicine,flowershavebeenchewedtorelieve toothacheandinfectionofthroatandtoparalyzethetongue(Dias etal.,2012;Lengetal.,2011).
Biological properties of A. oleraceae mainly depend on N-alkylamides, specially on spilanthol, the principal bioactive compoundwhichshowedimportantbioactivitiessuchas antioxi-dant,anti-inflammatory,ordiureticactivityandoralhealthcare(it hastraditionallybeenusedforthetreatmentoftoothache(Boonen etal.,2010).Otherimportantphytochemicalsinthisspeciesinclude alkaloids, flavonoids, saponins, steroid glycosides and tannins, whichwerealldetectedinthethree mainparts(leaf,stemand flower)ofA.oleraceae.Thephenolic contentsweresignificantly higherinleavesandflowerswhilethelowestvaluewasobserved
instems(leaf:7.59±1.26;flower:5.34±0.75;stem:1.65±0.35, resultsinmgofgallicacidequivalentsg−1drymatter).Thetotal antioxidantcapacity(TAC,inmgtroloxequivalentsg−1dry mat-ter)wasalsosignificantlydifferentamongleaf(5.29±0.85),stem (3.42±0.59)andflower(1.42±0.40).Thereportedresults repre-sent thescientific validation of the potentialuseof leavesand flowersintraditionalsystemsofmedicine(Abeysirietal.,2013; ShanthiandAmudha,2010).
4.3. ArtemisiaabsinthiumL.
A. absinthiumL.,commonlyknownaswormwood (Citronela-maior inPortugal)growsasaperennialherbwithfibrousroots onnon-cultivated, aridgroundor rockyslopesand attheedge of footpaths and fields. The plant is recognized by its charac-teristicodorwhich makesit usefulfor makingbiological sprays againstpests.Itisusedincompanionplantingtopreventweeds’ growing,sinceitsrootssecretesubstancesthatinhibitthegrowth of surrounding plants, besideshavingrepellant activityagainst insectlarvae.Itiscommonlyusedasaningredientin thespirit absinthe,andasaflavoringagentinsomeotherspiritsandwines. A.absinthiumhasbeenusedasherbalmedicinethroughoutEurope, Middle East,North Africa,and Asia.Theirhealtheffects include anti-helminthic,choleretic,antiseptic,balsamic,depurative, diges-tive,diureticandemmenagogueactivities,havingalsobeenusedin treatingleukemiaandsclerosis(Canadanovic-Brunetetal.,2005). Recently, theaerialpartof A. absinthiumhasshown anti-snake venomactivity,whileotherspeciesofthegenusArtemisiaexhibited antimalarialandanticanceractivities,amongotherprominent bio-logicaleffects(Canadanovic-Brunetetal.,2005;Nalbantsoyetal., 2013;Shafietal.,2012;Sharopovetal.,2012).
Besidesthebioactivityevaluationassays,different phytochem-icalswerealsocharacterized(Bailenetal.,2013;Leeetal.,2013). Thephenoliccompoundsinthewormwoodleavesextractwere identifiedandsalicylicacidwasthedominantphenoliccompound (≈14400.45gg−1 DW),followedbymyricetin(≈1086.55gg−1 DW), caffeicacid(≈80gg−1 DW),gallic acid(≈64gg−1 DW) andferulicacid(54gg−1DW).Otherdetectedcompoundswere quercetinandkaempferol(flavonols),ferulicacidando-coumaric acid(hydroxycinnamicacids),gallicacid,vanillicacid,-resorcylic acidandprotocatechuicacid(hydroxybenzoicacids).Therefore,the contentoftotalphenoliccompoundsintheextractsmightexplain theirhighantioxidant activities,especially in aqueous extracts, whichaccountedforthehighestantioxidantactivity,asevaluated through DPPH• scavengingactivity, reducing powerand Folin-Ciocalteuassays(Leeetal.,2013).
4.4. BidenspilosaL.
Bidenspilosa,commonlyknownas“hairybeggarticks,”“sticks tights,”and“Spanishneedles”iswidelydistributedinsubtropical andtropicalregionsandpresentstypicalyellowflowers.Theplant isusedinfolkmedicineforitsanti-inflammatory,antiseptic, liver-protective,anti-hypoglycemicandblood-pressureloweringeffects. IthasbeenwidelyusedinTaiwanasatraditionalmedicine,being alsothemajoringredientofanherbalinfusionthatisbelievedto preventinflammationandcancer(Dimoetal.,2002;Yangetal., 2006).
Themajor bioactivecomponentsfoundin Bidenspilosa con-tributingtoitsantioxidantactivityarephenylpropanoidglucosides, polyacetylenes,diterpenes,flavonoidsandflavoneglycosides.In addition, forty-four compounds, including the major terpenes -caryophyllene (10.9% and 5.1% in the leaves and flowers, respectively)and-cadinene(7.82%and6.13%intheleavesand flowers,respectively)were identifiedin theyellowish essential oilsobtainedfromitsfreshleavesandflowers(Krishnaiahetal.,
2011). These essential oils werereported as havingthe capac-itytoreducethestablefreeradicalDPPH•tothecorresponding diphenylpicrylhydrazinewithIC50 values of57 and 50gml−1, respectively,revealingthattheflowersofB.pilosahavean antioxi-dantactivitythatissimilartothatoftypicalsyntheticantioxidants (Debaetal.,2008).
4.5. CarthamustinctoriusL.
InPortugal,CarthamustinctoriusL.(commonlyknownas saf-flower)isparticularlyabundantintheSouth(EspeciallyinAlentejo province),whereit itsleavesareusedtoextractcolorantswith application in cooking and dyeing machinery, while the seeds areusedforcheesemanufacture.Regardingitsbiologicalactivity, C.tinctorius hasgradually beeninvestigated due toits medici-nalvalueandhealth careproperties,besideshavingawideuse intraditional Chinesemedicine.In addition,safflowerhasbeen usedasanherbalmedicineinKoreafor thepromotionof bone formationandinthetreatmentofosteoporosisandrheumatism. These properties are probably related to the serotonin deriva-tives,whichwereidentifiedasthemajorphenolicconstituentsof defattedsafflowerseeds.Thesecompoundshavebeenreportedfor theirstrongantioxidantactivityandbiologicaleffectsonplasma andliverlipidstatus,viabilityandgrowthofcancercelllinesor fibroblastsandcellularpro-inflammatorycytokineormelanin pro-duction(Baeetal.,2002;Choetal.,2004).Amongtheidentified derivatives,theserotoninalkaloids(e.g.,N-feruloylseretoninand N-p-cumaroylserotonin)arepotentinhibitorsofmelanin produc-tionsuggestingitspotentialuseasinhibitorsofmelanogenesis. Otherphenoliccompoundsincludethequinochalcones responsi-blefortheyellowandredfloralpigmentsanddifferentflavonoid glycosides,which,aswidelyrecognized,arecloselyrelatedtothe antioxidantactivity.Thequinochalconesandflavonoids,themajor antioxidantspresentinflowersofC.tinctorius(aqueousextracts), havebeenassessedinseveralstudiesfortheirabilitytoscavenge ROS(O2•−HO•,1O2)andDPPH•(Zhouetal.,2014).
4.6. InulacrithmoïdesL.
ThegenusInulaincludesmorethan100species,beingmainly foundinEurope,Africa,andAsia.Insomelocations,I.crithmoïdes isanimportantconstituentofthehumandiet.Youngleavesare eatenraworcookedandthefleshyleavesandyoungshotsare pick-ledandusedasarelishinsalads.ThefloweringbranchesofInula speciesareusedintraditionalmedicinefortreatmentofbronchitis, tuberculosis,anemia,malaria,urinarytractdiseases,andalsoasan astringent(Abdel-Wahhabetal.,2008;Fontanaetal.,2014).
Thedescribedbioactivitymightberelatedwiththehighlevels ofphenoliccompounds,characteristicoftheAsteraceaefamily,as thosedetectedintheacetonicextractsofI.crithmoïdes. Regard-ingitsantioxidantactivity,thisspeciesshowedhighpotentialas aDPPH• scavenger(IC50=12.8gml−1)and asaferricreducing agent(EC50=0.90mgml−1intheFRAPassay)(Jallalietal.,2014). 4.7. MatricariarecutitaL.
M.recutitaL.isanherbaceousplantindigenoustoEuropeand WesternAsia.Severalproductsderivedfromchamomileare com-merciallyavailableassoaps,detergents,fragrances,lotions,hair products,bakedgoods,confectionery,beveragesandinfusions.The consumptionofchamomile’infusionsisestimatedinmorethanone millioncupsperday(Maschietal.,2008;McKayandBlumberg, 2006).
Themainpharmacologicaleffectsaredeterminedbythe bio-logically active constituents, which include sesquiterpenic and phenolic compounds. Sesquiterpenic compounds such as
␣-bisabolol,bisabololoxidesAandB, chamazuleneandfarnesene, andphenoliccompounds(namelyapigenin,quercetin,patuletin, and luteolin,and theirglucosides,and thecoumarins herniarin andumbelliferone),areconsideredtobethemajorbioactive com-poundsofchamomile.Sesquiterpeniccompoundsarewidelyfound intheessentialoilsofseveralplantsandfruits,providinga pro-fusespectrumofaromas,mostlyperceivedasverypleasant(Barros etal.,2010;Guimarãesetal.,2013;McKayandBlumberg,2006; Salamon,2007;Srivastavaetal.,2010).
SeveralbiologicaleffectshavebeenattributedtoM.recutitaL., suchasanti-microbial,antioxidant,anti-malarial,anti-mutagenic, anti-platelet,anti-cancer,anti-inflammatory,anti-genotoxic, anti-spasmolytic, sedative and hypocholesterolemic. Furthermore, it has interesting gastrointestinal, hepatic and topical properties. Some of its commonuses include flatulentnervous dyspepsia, travelsickness, nasalcatarrh, restlessness,gastro-intestinal dis-ordersassociatedwithnervousirritability,hemorrhoids,mastitis, legulcer,renalcolic,nausea,constipation,expulsionofparasitic worms,stomachcomplaintsand skindiseases.Theessential oil ofchamomilerevealedanti-inflammatory,anti-bacterial, antimy-cotic, and ulcer-protective properties (Guimarães et al., 2013; McKayandBlumberg,2006;Petronilhoetal.,2012).The antioxi-dantactivityofM.recutitahasbeenobjectofseveralstudies,either itswholeextracts,orisolatedcompoundssuchaschamazulene, nerolidoland␣-bisabolol, particularlyitsscavengingactivityby DPPH• and TBARSformationinhibition (Petronilhoet al.,2012; Robyetal.,2013).
4.8. OtanthusmaritimusL.
OtanthusmaritimusL.istheonlyspeciesofthemonotypicgenus Otanthus.Thisspecieslivesonmaritimesandsalongthecoastsof SouthandWestEurope,northwardstoSouth-EastIreland.Theuse ofO.maritimushasbeenreportedintraditionalmedicine, specifi-callyinthetreatmentoftoothache,asthmaticbronchitis,dysentery andbladderinflammation(Cabralet al.,2013;Tsoukatouetal., 2000).
Different studies reportthe isolation of severalcomponents fromtheaerial partsof O. maritimus:flavonoids, sesquiterpene lactones,monoterpenes,lignanesandamides.Therootscontain fattyacidamides,acetylenederivativesandsesquiterpenes.Over 30compoundshavebeenidentifiedinessentialoils,withaprimary emphasisonchrysanthenone(40.4–57.2%),filifolone(12.2–15.5%), cis-chrysantenyl acetate (10.1–11.2%) and ␣-pinene (6.7–7.2%) withanti-fungalandanti-inflammatoryactivity.Chrysanthenone, themaincompoundofO.maritimusessentialoil,isararebicyclic monoterpeneketonewithaslightlyoily-floralaromasuitablefor aromaticindustry,beingfoundonlyinmembersoftheAsteraceae family(Cabraletal.,2013;Musellietal.,2007;Ruiuetal.,2013). 4.9. PartheniumhysterophorusL.
Partheniumhysterophorus,alsoknownascongressgrass,isan invasiveweed withhighdisseminationin India,butwhich can befound allover the world.All parts of theplantare used in traditionalmedicineasbittertonic,febrifuge,emmenagogue, anti-dysenteric and treatment of many infectious and degenerative diseases(Kumaretal.,2013;Reddyetal.,2011).
Recentstudieshaveidentifiedandquantifiedthemajor bioac-tive compounds present in flowers and roots extracts of P. hysterophorus:flavonoids,terpenoids,alkaloidsandcardiac glyco-sides.Thetotalphenolic contentwasalsoassessedinthesame extracts,whichshoweda highscavengingcapacity againstHO• andabilitytoprotectthelipidmembranefromperoxidation. Fur-thermore,P.hysterophorushasbeenreportedforitspotentialto
neutralizethefreeradicalinducedoxidativedamage,antibacterial activityandcytotoxicpotential(Kumaretal.,2013,2014).
5. Conclusion
TheAsteraceaefamilyhasaworldwidedistributionwithhigh representationinthePortugueseterritory.Inrecentyears,the sci-entificcommunity,food,pharmaceuticalandcosmeticindustries haveshownanincreasinginterestinthestudyandapplicationof plantsextracts,inthedevelopmentofnewandimproved func-tional,preventiveorcurativeproducts,especiallythosededicated tosolvethespecific demandsofrecurrent illnesses.A common underlyingmechanismoftheseailmentsistheproduction(or exac-erbation ofproduction) of reactivespecies inthe humanbody, whichisdirectlyorindirectlyrelatedtocardiovascularand neu-rodegenerative,cancer,aging, eyeproblems,among others.The bioactivecompoundsproducedbyplants,suchasthosebelonging toAsteraceaefamily,andtheirrecurrentuseintraditionalmedicine boostedthedevelopmentofappliedstudiestoattesttheir benefi-cialproperties,namelytheirhighbioactivitylevels.
AlthoughmanyAsteraceaespecieswerealreadystudiedfor dif-ferentproperties,thespecieswithhigherrelevancearestillscarcely studied,justifyingfurtherexplorationoftheirpotentialbioactivity, allowingtoimprovetheknowledgeontheuseoftheirextractsfor medicine,pharmaceutical,foodandcosmeticindustry.Thework reportedherein,highlightstheplantswithhighestpotentialtobe furtherstudied,especiallyconcerningtheirmostrelevant bioac-tive properties and important bioactive compounds that could bepurifiedfollowingtop-of-the-artmethodologies.Theacquired knowledgecouldbeusedinextensionapplications,suchasthe incorporationofextracts/isolatedcompoundsindifferentproduct types,inresponsetothegrowinginterestofsuchresources,aswell astheimportanceofcontributingtothesustainabledevelopment ofacountrywithsuchanhighbiodiversity.
Acknowledgments
João C.M. Barreira is grateful to Fundac¸ão para a Ciên-cia e a Tecnologia (FCT) for his post-doctoral research grant (SFRH/BPD/72802/2012),financedbyPOPH-QRENandsubsidized byFSEandMCTES.Thisworkreceivedfinancialsupportfromthe EuropeanUnion(FEDERfundsthrough COMPETE)andNational Funds(FCT)throughprojectPest-C/EQB/LA0006/2013.Thework alsoreceivedfinancialsupportfromtheEuropeanUnion(FEDER funds)undertheframeworkofQRENthroughProject NORTE-07-0124FEDER-000069.
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