Review ArticleTraditional Uses Chemical Constituents and BiologicalActivities of Bixa orellana L A Review
Daniela de Arauacutejo Vilar1 Marina Suecircnia de Araujo Vilar1
Tuacutelio Flaacutevio Accioly de Lima e Moura2 Fernanda Nervo Raffin2 Maacutercia Rosa de Oliveira3
Camilo Flamarion de Oliveira Franco4 Petrocircnio Filgueiras de Athayde-Filho5
Margareth de Faacutetima Formiga Melo Diniz1 and Joseacute Maria Barbosa-Filho1
1 Laboratory of Pharmaceutical Technology Federal University of Paraıba 58051-900 Joao Pessoa PB Brazil2 Department of Pharmacy Federal University of Rio Grande do Norte 59010-180 Natal RN Brazil3 Department of Molecular Biology Federal University of Paraıba 58051-900 Joao Pessoa PB Brazil4 State Company of Agricultural Research of Paraıba Rua Eurıpedes Tavares 210 Tambia 58013-290 Joao Pessoa PB Brazil5 Department of Chemistry Federal University of Paraıba 58051-900 Joao Pessoa PB Brazil
Correspondence should be addressed to Jose Maria Barbosa-Filho jbarbosaltfufpbbr
Received 11 February 2014 Revised 17 May 2014 Accepted 31 May 2014 Published 23 June 2014
Academic Editor Tsutomu Hatano
Copyright copy 2014 Daniela de Araujo Vilar et alThis is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in anymedium provided the originalwork is properly cited
Bixa orellana L popularly known as ldquourucumrdquo has been used by indigenous communities in Brazil and other tropical countries forseveral biological applications which indicates its potential use as an active ingredient in pharmaceutical products The aim of thiswork was to report the main evidence found in the literature concerning the ethnopharmacology the biological activity and thephytochemistry studies related to Bixa orellana LTherefore this work comprises a systematic review about the use of Bixa orellanain the American continent and analysis of the data collectedThis study shows the well-characterized pharmacological actions thatmay be considered relevant for the future development of an innovative therapeutic agent
1 Introduction
The use of natural compounds of mineral animal or plantorigin in food products cosmetics and drugs began long agoThere are written records of ancient Egyptian and Chinesecivilizations that havemade use of these products Nowadaysthere has been a return to the search for products calledldquonaturalrdquo which in fact never ceased to exist The analysisof the composition of many drugs shows that almost 50of those in clinical use are derived from natural compoundsFurthermore not only plants but also plant byproducts arewidely used as preservatives andflavoring and coloring agentsin various food and cosmetic preparations [1]
Bixa orellana is a plant native to Brazil but grows in otherregions of South and Central America It is grown in tropicalcountries such as Peru Mexico Ecuador Indonesia IndiaKenya and East Africa [2]
The seeds of this plant produce one of the dyes mostfrequently used worldwide not only in food products butalso in the textile paint and cosmetic industries Its use hasbeen stimulated due to the ban on the use of synthetic dyesin food and cosmetics where it is one of the few acceptedby theWorld Health Organization (WHO) since in additionto being nontoxic it does not seem to change the food value[3] Another interesting fact is that 70 of all natural coloringagents consumed worldwide are derived from annatto [4]
Annatto first spread in the form of food coloring alsoknown as paprika a condiment widely used in cooking toenhance the color of food Today however its use has spreadinto many segments of industrial production Thus it is nowapplied on the skinmdashin the form of makeup and sunscreenmdashand there is research proving that its use brings healthbenefits which makes producers thankful for cultivating it[5 6] Therefore in the continuation of our research on
Hindawi Publishing Corporatione Scientific World JournalVolume 2014 Article ID 857292 11 pageshttpdxdoiorg1011552014857292
2 The Scientific World Journal
bioactive molecules from various species of different plantfamilies [7ndash22] we offer this compilation of the traditionaluses chemical constituents and biological activities of Bixaorellana
The aim of this review is to highlight the biologicaland phytochemical studies that have been published aboutBixa orellana in South and Central America and try tocorrelate these studies with the popular uses of this plantin those regions as well as to evaluate whether its chemicalcomposition can support the reported biomedical propertiesrelated to Bixa orellana
2 Materials and Methods
In this work the biological activities and compounds isolatedfrom Bixa orellana were searched using the database ofthe Web of Science Scielo and the University of Illinoisin Chicago NAPRALERT (acronym for ldquoNAturalPRoductsALERTrdquo) The data were updated in April 2014 using ldquoBixaorellana chemical and bixinrdquo as keywords for this reviewThereferences found in the survey were later consulted for detailsabout the models or mechanisms of bioassays used to test theextracts of Bixa orellana
3 Botanical
The annatto tree belongs to the family Bixaceae and thegenus Bixa Despite the existence of several species the mostcommon in our country is Bixa orellana L named afterFrancisco Orellana who was the first European to navigatethe Amazon [23]
According to Revilla [58] B orellana is a small tree orshrub measuring from 3 to 5 meters in height sometimesreaching a height of 10 meters The trunk is short measuring20ndash30 cm in diameter with dark gray bark with lenticels invertical rows The leaves are alternate 10 to 20 cm long and 5to 10 cm wide sharp green on both sides and with extendedpetioles
According to Oliveira et al [59] seeds measure 03ndash05cm in length and 02-03 cm in diameter and their shapevaries frompyramidal to almost conicalThe number of seedsper capsule varies according to the author Alonso [60] foundthat each bivalvar capsule may contain from 30 to 60 seedson average
The seeds are considered the plant part of commercialimportance since the pericarp (layer that surrounds theseeds) contains the pigments that have wide industrial appli-cation About 80 of this pigment is the carotenoid known asbixin which has the dye property and can be extracted withvegetable oils or chemical bases Depending on the cultivarand climatic conditions of the region the bixin content canvary from 1 to 6 in the seed arilThe remainder is composedof other dyes and inert substances of minor importance [61]
4 Use in Traditional Medicine
Annatto is a native plant from South America more specif-ically of the Amazon region The popular name ldquourucumrdquo
comes from the Tupi word ldquoru-kurdquo which means ldquoredrdquo InBrazil this plant is commonly known as urucum urucuacafrao acafroa and acafroeira-da-terra It is known by otherpopular names in other countries atole achiote and bija(Peru and Cuba) axiote (Mexico) achiote achote anattobija and santo-domingo (Puerto Rico) bixa (Guyana) analto(Honduras) guajachote (El Salvador) onotto and onotillo(Venezuela) achiote and urucu (Bolivia) urucu (Argentina)roucou (Trinidad) roucou and koessewee (Suriname) andannatto (United States) The wide dissemination of its usein those regions is related to the growing demand fornatural dyes by many pharmaceutical cosmetic textile andespecially food industries [57]
According to Correa [27] seeds urucum supplies seedsthat have been used as a condiment as well as laxativecardiotonic hypotensive expectorant and antibiotic Inaddition it has anti-inflammatory activity for bruises andwounds and has been used for the treatment of bronchitis andfor wound healing purposes Oil is also obtained from thisplantThe infusion of the leaves has been shown to be effectiveagainst bronchitis sore throat and eye inflammation Thepulp which includes the seed is used for soft drinks andfebrifuge Moreover it can provide valuable dyeing materialssuch as yellow (orellin) and red (bixin) substances with thelatter constituting a crystallized active ingredient
In the food industry it is used to color butter margarinemayonnaise sauces mustard sausage soup juice ice creambakery productsmacaroni and cheese where it is commonlycalled ldquodo reinordquo (of the kingdom) coming from HollandIt is also widely used in the printing industry and dyemanufacturing Many Aborigines use annatto for dyeingwhere the dye is naturally obtained as a mixture and used tocolor ceramics and other vases for domestic use In additionmost endogenous people use this dye on their skin to beautifythemselves during religious rituals and mainly to protectthemselves from ultraviolet radiation and from mosquitoesthat infest forests [49] The bast provides fibers for roughcordage and the powder resulting from grinding the seedshas been used as an aphrodisiac Finally the infusion of coldbuds serves to wash inflamed eyes whereas the decoctionof the leaves has been used for antiemetic therapy duringpregnancy [27] (Table 1)
Thus despite the different culture and traditions amongthe countries in South and Central America several ofthe popular uses of Bixa orellana are the same for exam-ple antipyretic aphrodisiac antidiarrheal antidiabetic andinsect repellent
5 Chemical Compounds
Bixin a red-colored carotenoid is the pigment present inhigh concentration in the annatto seed aril It is the mainsubstance responsible for the dyeing characteristics of seedswhere its concentration can be as high as 50 Howeverdifferent seeds may have levels less than 20 and becausetheir commercial value is based on the bixin percentage levelshigher than 25 are usually required for export [61]
The Scientific World Journal 3
Table 1 Traditional uses of annatto in American countries
Countryuse Plant part ReferencesArgentina
Antipyreticcardiotonicantidiarrheal Seeds [24]Antidiarrhealdyescondiment Seeds [25]
BrazilBody paint Seeds [26]Insect repellent Seeds [27]Condimentfood coloring Seeds [27]Antipyretic Seeds [26]Antipyreticlaxativesburns Seeds [28]Malaria Seeds [26]
ColombiaSnakebite Leaves [29]Aphrodisiac Seeds [30]
CubaAphrodisiac Seeds [31]
GuatemalaGonorrheadysentery Leaves [32]Hepatitis Leaves [33]Dysentery Leaves [34]Blood diseases Leaves [35]Gonorrhea Roots [32]Diabetes Roots [36]
HondurasAromaticfood coloring Seeds [37]Paindigestivedysentery Leaves [38]
JamaicaDiabetes Seeds [39]
NicaraguaRespiratory and pulmonary disordersdiarrheadiureticburns Leaves + seeds [40]Labor pains Seeds [41]Coughcolddiureticdiarrheaburnslabor pains Seeds [40]
ParaguayInsecticiderepellent Seeds [42]Diabetes Seeds [39]
PeruAphrodisiacaphrodisiacdiureticantidisenteriaastringent Fruits [34]Antipyreticskin problems Leaves [33]Alcoholic hepatitisworms Roots [33]Antipyreticaphrodisiacdysenteryastringentstomach Seeds [34]
Trinidad and TobagoDiuretic Leaves [43]Diabetes Roots [44]Diabetes Roots [45]
Bixin was isolated for the first time from the seeds of Bixaorellana in 1875 and in 1961 its complete chemical structureand stereochemistry were determined by 1H and 13C-NMRBixin belongs to the small class of natural apocarotenoidswhose formation occurs by the oxidative degradation of C40carotenoids (Table 2)
Bixin consists of a chain of 25 carbons and has the molec-ular formula C
25H30O4(MW = 39451) It has a carboxylic
acid and methyl ester group at the ends of the chain Bixinoccurs in nature as 16-119885 (119888119894119904) but during the extractionprocess it isomerizes resulting in the 16-119864 form (trans) whichis called isobixin (Figure 1)
4 The Scientific World Journal
Table 2 The main carotenoids from the seeds of Bixa orellana
Carotenoid Country of isolation Physical aspect ReferencesApo-120595-carotene 91015840Z-61015840-ol Brazil Oil [46]
Beta carotene Brazil 183∘C [47]Suriname lowast [48]
Bixin
Brazil 198∘C [49ndash51]Peru lowast [52]
Dominican Rep lowast [53]Suriname lowast [48]USA lowast [54]
Z-Carotene Brazil Oil [46]Cryptoxanthin Suriname 173∘C [48]Dimethyl-(9Z)-661015840-diapocarotene-661015840-dioate Brazil Oil [52]Dimethyl-(9Z91015840Z)-661015840-diapocarotene-661015840-dioate Brazil Oil [50]Phytoene Brazil Oil [46]Phytofluene Brazil Oil [46]Geranylgeraniol Brazil Oil [52]Lutein Suriname 196∘C [48]Methyl-(9Z)-101015840-oxo-6101015840-diapocarotene-6-oate Brazil Oil [50]Methyl-(9Z)-61015840-oxo-651015840-diapocarotene-6-oate Brazil Oil [50]Methyl-(9Z)-81015840-oxo-681015840-diapocarotene-6-oate Brazil Oil [50]Methyl-(91015840Z)-apo-61015840-lycopenoate Brazil Oil [46]Methyl-(7Z9Z91015840Z)-apo-61015840-lycopenoate Brazil Oil [55]Methyl-(9Z)-apo-81015840-lycopenoate Brazil Oil [46]Methyl-(all-E)-apo-81015840-lycopenoate Brazil Oil [46]Neurosporene Brazil Oil [46]Norbixin Brazil 300∘C [52]Trans-bixin Jamaica 195∘C [56]Zeaxanthin Suriname 215∘C [48]Source [57]
Many other carotenoids (C19 C22 C24 C25 C30 and C
32)
occur in Bixa orellana but constitute a minor percentage ofthe pigments The major oily constituent of annatto seedsis geranylgeraniol representing 1 of dry seeds Norbixin(Figure 1) is a demethylated derivative of bixin and althoughit is a naturally occurring compound it is almost alwaysreferred to as a saponification product of bixin This is theform used for commercial purposes [62]
Currently more than two dozen substances have beenisolated from the seeds of Bixa orellana Besides bixin andnorbixin other compounds such as isobixin beta-carotenecryptoxanthin lutein zeaxanthin orellin bixein bixol cro-cetin ishwarane ellagic acid salicylic acid threonine tomen-tosic acid tryptophan and phenylalanine have been found inthe seeds of annatto In addition the following compounds intheir respective concentrations are found in these seeds 40to 45 cellulose 35 to 55 sugars 03 to 09 essential oils3 fixed oils 10 to 45 pigments and 13 to 16 proteinsand alpha and beta-carotene as well as tannins and saponins[63 64]
Mercadante et al [50 65] isolated eight apocarotenoidsfromannatto seedsmethyl (7Z 9Z 91015840Z)-apo-61015840-lycopenoatemethyl (9Z)-apo-81015840-lycopenoate methyl 1(all-E)-apo-81015840-lycopenoate methyl (all-E)-8-apo-beta-carotene-81015840-oate
methyl (all-E)-apo-61015840-lycopenoate 6-geranylgeranyl-81015840-methyl-681015840diapocaroten-6-81015840dioate 61015840-geranylgeranyl-61015840-methyl-(9Z)-661015840-diapocaroten-6-61015840-dioate and 6-geranylgeranyl-61015840-methyl-6-61015840-diapocaroten-6-61015840-dioate
More than 100 volatile compounds have been detectedin aqueous and organic extracts where 50 of these havealready been identified (eg bornyl acetateprop-caryophyllenecopaene prop-cubebene (+)-cyclosativene geranyl phenylac-etate 1-heptanetiol 3-methylpyridine 4-methylpyridine 120574-elemene 120573-humulene isoledene 120573-pinene seline-6-en-4-ol120575-selinene (minus)-spathulenol and (+)-ylangene) [66]
Because annatto is a rich source of carotenoids it isof great commercial importance In fact the therapeuticproperties of annatto (eg antioxidant and hypoglycemic)have been attributed to its high levels of carotenoids [67ndash69]Table 2 lists some of these compounds
The pigments in annatto seeds can be extracted bymechanical processes through grinding the seeds and byphysical-chemical methods using solvents or enzymes [46]The solvent extraction can be performed using three basicmethods alkaline extraction (NaOH or KOH solutions)which results in the conversion of bixin to norbixinextraction with oil (soybean corn) and extraction usingorganic solvents (hexane chloroform ethanol acetone or
The Scientific World Journal 5
Bixin (Z-bixin or cis-bixin)
COOH
COOMe
116
(a)
MeOOC 16 1
Isobixin (E-bixin or trans-bixin)
COOH
(b)
COOHHOOC
Norbixin
(c)
OH
Geranylgeraniol
(d)
Figure 1 Chemical structure of some pigments of annatto
propylene glycol) which results in the purest form of pig-ments
Barbosa-Filho et al [49] studied the seeds of four typesof annatto cultivated in Paraıba State Brazil namely ldquocas-caverderdquo (ldquogreen peelrdquo) ldquocascavermelhardquo (ldquored barkrdquo) ldquobicode calangordquo (ldquolizard beakrdquo) and ldquograopretordquo(ldquoblack grainrdquo)with respect to their oil (material extracted with hexane)and solid (material extracted with chloroform) contentsand also pure bixin which was obtained by successiverecrystallization from the chloroform fraction Pure bixinappears as red-purple crystals with a melting point of 196ndash198∘CThe different concentrations found for the oil fractionchloroform extract and bixin are as follows red bark 58lizard beak 51 green peel 49 and black grain 46 Redbark shows the highest yield for both solvent fractions andthe bixin amount is around 1This species has been reportedas the most used in folk medicine On the other hand blackgrain shows negligible amounts of bixin
6 Biological Activity
Table 3 shows data found in 38 studies performed withannatto in 15 different countries in the American countriesTo obtain the extracts and fractions tested several plant partswere used such as leaf root seed shoot and even the wholeplant The data surveyed were classified according to thepharmacological activity tested
Among the twenty-one activities tested those with thelargest number of studies performed were antifungal activity(12) antibacterial activity (12) antimalarial activity (6) andmutagenic activity (3) Cytotoxic activity and toxicity havebeen little studied with three and two studies respectivelyPharmacological activities have been evaluated in animalmodels (22 preclinical studies) human models (1 clinicalstudy) cell cultures (2 studies) and in vitro tests (32 studies)
Antifungal activity has been investigated in one countryin Central America (Guatemala) and in two countries inSouth America (Ecuador and Argentina) using eleven differ-ent fungal strains [70 82 84]
Freixa et al [82] conducted a study in Ecuador to assessthe antifungal activity of extracts from the dried leaves of
the annatto tree in response to 7 fungi species obtainingsatisfactory antifungal activity against Trichophyton menta-grophytes trains In Guatemala three different strains wereused to evaluate antifungal activity with no satisfactoryactivity being observed [84]
The extracts of annatto leaves have been evaluated forantibacterial activity against 8 different bacterial strains(Bacillus subtilis Escherichia coli Micrococcus luteus Pseu-domonas aeruginosa Staphylococcus aureus Salmonella typhiShigella dysenteriae and Staphylococcus epidermidis) show-ing no activity
Antimalarial activity has been determined against Plas-modium gallinaceum Plasmodium lophurae andPlasmodiumberghei Although the studies conducted previously in theUnited States did not show significant results [92] Valdes etal (2011) reported a moderate activity of the seed extracts ofBixa orellana against Plasmodium berghei and falciparum
7 Mutagenic and Cytotoxic Activities
No significant effect was observed when extracts of annattoseeds were tested for mutagenic activity in studies performedin the United States and Brazil [67 93]
Extracts obtained from annatto seeds and leaves havebeen tested in cell cultures and the brine shrimp assayrespectively and have been found to lack cytotoxicity ineither model used These experiments were carried out inGuatemala and the Dominican Republic [83 89]
On the other hand a study performed in Cuba with 10medicinal plants that were active in inhibiting human lungcarcinoma cell growth showed that the ethanolic extract ofBixa orellana presented cytotoxicity at concentrations below100 120583gmL [81]
8 Toxicological Activities
Currently concerns about the effect of synthetic dyes onhuman health are incontestable making people increasinglychoose those of natural origin believing that they are devoidof toxic effects This is not entirely true because even amedication from a natural source can be a poison depending
6 The Scientific World Journal
Table3Biologicalactiv
ities
ofextractsof
annatto
inAmerican
coun
tries
Cou
ntry
biologicalactiv
ityPartused
Type
ofextract
Organism
teste
dMod
elteste
dDoseu
sed
Activ
ityRe
ferences
Argentin
aAntibacteria
lLE
EtOH
Bacillussubtilis
Invitro
5mgmL
Inactiv
e[70]
Escherich
iacoli
Invitro
5mgmL
Inactiv
e[70]
Micrococcusluteus
Invitro
5mgmL
Inactiv
e[70]
Pseudomonas
aeruginosa
Invitro
5mgmL
Inactiv
e[70]
Staphylococcus
aureus
Invitro
5mgmL
Inactiv
e[70]
Antifu
ngal
LEEtOH
Aspergillus
niger
Invitro
5mgmL
Inactiv
e[70]
Cand
idaalbicans
Invitro
5mgmL
Inactiv
e[70]
Antivira
lSE
EtOH
VirusH
erpessim
plex
1Cell
cultu
re078
mgmL
Inactiv
e[71]
Insecticidal
AP
MeO
HInsect
Sitophilu
soryzae
5Inactiv
e[71]
Brazil
Antim
alarial
SECH
Cl3
Mou
sePlasmodium
berghei
100m
gkg
Inactiv
e[26]
Antioxidant
SEEtOH
Invitro
DPP
Hassay
01g
Lminus1
Activ
e[6]
Insectrepellent
SEPetr
eth
Ham
ster
Lutzom
yialongipalpis
1gL
Activ
e[72]
SEEtOH
Mosqu
itoAe
desa
egypti
182mgmL
Activ
e[6]
Molluscicidal
SEEtOH
Con
chBiom
phalariagla
brata
10000
ppm
Inactiv
e[73]
Mutagenic
Powder
Mou
seBo
nemarrowcells
10670
ppm
Inactiv
e[67]
Toxicity
SEPo
wder
Rat
Invivo
500m
gkg
Inactiv
e[74]
Antileish
manial
LERO
EtOH
Leish
maniaam
azonensis
Invitro
012ndash25mgmL
Activ
e[75]
Antileish
manial
SEOE
Leish
maniaam
azonensis
Invitro
10501005001000120583gmL
Activ
e[76]
Hyperlip
idem
iaSE
H2O
Mou
seIn
vitro
400and800m
gkg
Activ
e[77]
Colom
bia
Snakebite
LEEtOH
Mou
seBo
throps
atrox
LD50gt260120583
ganim
alAc
tive
[29]
CostaRica
Anti-infl
ammatory
ROEtOH
Rat
Pawedem
acarrageenan
100m
gkg
Inactiv
e[78]
Cuba Positiveino
tropice
ffect
AP
H2O
Guineap
igIsolated
atriu
m320120583
LInactiv
e[79]
Antim
alarial
SEPlasmodium
gallina
ceum
falciparum
Invivoin
vitro
500m
gkg
Activ
e[80]
Cytotoxic
SEEtOH
Tumor
cells
Invitro
39ndash
250m
gmL
Activ
e[81]
Ecuado
rAntifu
ngal
LEMeO
HAspergillus
niger
Invitro
10mgdisk
Inactiv
e[82]
Cand
idaalbicans
Invitro
10mgdisk
Inactiv
e[82]
Cryptococcus
neoforman
sIn
vitro
10mgdisk
Inactiv
e[82]
Fusariu
moxysporum
Invitro
10mgdisk
Inactiv
e[82]
Neurospora
crassa
Invitro
10mgdisk
Inactiv
e[82]
Penicilliu
mpurpurogenum
Invitro
10mgdisk
Inactiv
e[82]
Trich
ophytonmentagrophytes
Invitro
10mgdisk
Activ
e[82]
The Scientific World Journal 7
Table3Con
tinued
Cou
ntry
biologicalactiv
ityPartused
Type
ofextract
Organism
teste
dMod
elteste
dDoseu
sed
Activ
ityRe
ferences
Guatemala
Antibacteria
lLE
Vario
usEscherich
iacoli
Invitro
50120583Ldisk
Inactiv
e[83]
Pseudomonas
aeruginosa
Invitro
MICgt10mgmL
Inactiv
e[83]
Salm
onellatyphi
Invitro
MICgt10mgmL
Inactiv
e[83]
Shigelladysenteriae
Invitro
50120583L
Inactiv
e[83]
Staphylococcus
aureus
Invitro
MICgt10mgmL
Inactiv
e[83]
Antifu
ngal
LEH
2OAspergillus
flavus
Invitro
MICgt10mgmL
Inactiv
e[84]
Cand
idaalbicans
Invitro
MICgt10mgmL
Inactiv
e[84]
Microsporum
gypseum
Invitro
MICgt10mgmL
Inactiv
e[84]
Antigon
orrheal
LEEtOH
Neisseriagonorrhea
Invitro
50120583Ldisk
Activ
e[32]
Antitrypanosom
alLE
EtOH
Trypanosom
acruzi
Invitro
MICgt1m
gmL
Inactiv
e[83]
Cytotoxic
LEH
2OCr
ustacean
Artemiasalin
aLC
50gt10
00pp
mInactiv
e[83]
Inhibof
plateletaggregation
SE
Invitro
Thrombinaggregation
IC50
0795m
gmL
Inactiv
e[35]
Haw
aii
Con
traceptiv
eRO
Mou
se
02m
Lanim
alInactiv
e[85]
Jamaica
Hypoglycemic
SECH
Cl3
Dog
1gAc
tive
[39]
H2O
Dog
200m
Lanim
alAc
tive
[39]
Antioxidant
SEEtOH
Invitro
Invitro
025
and25120583
gmL
Activ
e[86]
Mexico
Allergenic
SEOil
Hum
an25120583L
person
Activ
e[87]
Paragu
ayInsecticidal
SEPetr
ether
Insect
Rhodnius
negle
ctus
50120583g
Inactiv
e[42]
Puerto
Rico
Molluscicidal
TPH
2OCon
chLymna
eacubensis
LD100gt1M
ppm
Inactiv
e[88]
Dom
inican
Repu
blic
Cytotoxic
SEEtOH
Cellculture
Molt4
cells
200120583
gmL
Inactiv
e[89]
Trinidad
andTo
bago
Antibacteria
lSE
EtOAc
Escherich
iacoli
Invitro
1000120583gmL
Inactiv
e[90]
Pseudomonas
aeruginosa
Invitro
1000120583gmL
Inactiv
e[90]
USA A
nticon
vulsa
ntRA
EtOH
Mou
seSeizureselectroshock
100m
gkg
Inactiv
e[91]
Rat
Seizurespentylenetetrazole
400m
gkg
Inactiv
e[91]
Antim
alarial
SECH
Cl3
Chicken
Plasmodium
gallina
ceum
388m
gkg
Inactiv
e[92]
Mutagenic
SEMeO
HSalm
onellatyphim
urium
100m
gplaque
Inactiv
e[93]
H2O
Invitro
Placentaltroph
oblasts
100m
gplaque
Inactiv
e[93]
Hypotensiv
eRA
EtOH
Rat
50mgkg
Activ
e[93]
Toxicity
RAH
2OMou
seLD
50gt700m
gkg
Inactiv
e[92]
LEleafAP
aeria
lpartTP
totalplantRO
roo
tSE
seedno
tgivenLD5050
lethaldo
seIC5
0concentrationthatinhibits50of
thee
ffectM
ICm
inim
uminhibitory
concentration
8 The Scientific World Journal
on the dose that is administered The failure to require in-depth data related to toxicological and chemical analysesfor the registration of food additives derived from naturalsources [67 74] certainly makes the information aboutpossible unwanted effects andor pharmacological activitiesresulting from their use much rarer than expected in view ofthe importance of the topic In Brazil the use of annatto is sowidespread that its safety is not even questioned
Paumgartten et al [91] evaluated the toxicity of annattoextracts in rats Doses up to 500mgkg body weightdaywere introduced directly into the stomach of pregnant ratsto evaluate the effect on the mother and fetus and noadverse effects were found for either The annatto extract didnot induce an increase in the incidence of visible externalvisceral or skeletal anomalies in the fetuses Therefore thestudy suggested that the annatto extract was not toxic to ratsnor was it embryotoxic Studies performed in Brazil by Alvesde Lima et al [67] where extracts of annatto weremixed withthe food of male rats showed that the concentrations testedhad no mutagenic or antimutagenic activity in their bonemarrow cells A parallel toxicity study conducted byHagiwaraet al [74] showed that 01 annatto extract administered forthirteen weeks in the feed of male and female rats did notshow any adverse effects However when higher doses wereadministered (03 and 09) the authors noticed an increasein liver weight as well as changes in blood chemistriesincluding increase in alkaline phosphatase phospholipidsand total protein as well as albumin and albuminglobulinratio
Hagiwara et al [74] also evaluated extracts of annattofor liver carcinogenicity in rats and found no evidence ofliver tumors even when given to animals at a high dose of200mgkg body weightday compared to an acceptable doseof 00 to 0065mgkgday thus indicating that the dangerof a hepatocarcinogenic effect in humans may be absent ornegligible
A toxicity test was performedwith extracts obtained fromboth plant seeds and shoots and no significant effect wasobserved The experiments were performed in the UnitedStates using mice as the animal model and it was found thatthe LD50 was greater than 700mgkg [92]
9 Correlation between the BiologicalActivities Phytochemistry and theTraditional Uses of Bixa orellana
Table 1 shows that many of the traditional uses of Bixaorellana are the same in several countries of South andCentral America which suggests its effectiveness as a ther-apeutic agent Extracts of Bixa orellana showed biologicalactivities such as antioxidant hypotensive molluscicideand antimalarial against A549 cells for carcinoma of thelung allergy hypoglycemic antifungal antioxidant insectrepellent antigonococcal and antivenom serum and some ofthem are in accordance with the traditional use for examplein Brazil it is used to extract the seeds with purpose repellentinsecticide and antimalaria and scientific studies in the samecountrywith the Lutzomyia longipalpis insect repellent action
and prove a study in Cuba proved the pharmacological actionfor antimalarial activity when tested against Plasmodiumberghei Some of them are in accordance with the traditionaluse for example seed extracts have been used in Brazil andCuba as insect repellent and antimalarial Antioxidant andinsect repellent activities can be attributed to the carotenoidsand the essential and fixed oils respectively
Despite the previous reports about the presence of com-ponents with anti-inflammatory properties such as salicylicacid lutein polyphenols and tannins this activity has not yetbeen proven for Bixa orellana extracts Similarly the plantrsquosessential and fixed oils have shown antibacterial propertiesalthough this activity has not been proven too
In general the data obtained in this review do not allowcorrelations between the biologic activities tested in vitro or invivo with the compounds identified in this species Howevertaking into account the related activities such as the antipara-sitic effect and the lack of mutagenic and cytotoxicity activityit is possible to consider Bixa orellana as a potential source forthe development of phytopharmaceutical products
In conclusion the studies discussed in this review repre-sent a rich database around the Bixa orellana activities andits potential uses which evokes the feasibility of phytophar-maceuticals to treat some diseases whenever an antioxidanthypotensor or hypoglycemiant activity is necessary
Although the commercial exploitation of this species iswell established there are very few studies on its pharma-cological effects Considering the need for developing a safeand effective product more studies should be performed inorder to confirm other biological activities supported by thepopular uses of Bixa orellana
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors are grateful to CNPqPRONEXFAPESQ andCAPES for financial support and to the NAPRALERTDatabase of the University of Illinois USA for the literatureon Bixa orellana A Leyva helped in editing the Englishlanguage of the paper
References
[1] M B Perecin O A Bovi and N B Maia ldquoPesquisa complantas aromaticas medicinais corantes o papel do InstitutoAgronomicordquo O Agronomico vol 54 pp 21ndash24 2002
[2] M E A Elias G Schroth J L V Macedo M S S Motaand S A DrsquoAngelo ldquoMineral nutrition growth and yields ofannatto trees (Bixa orellana) in agroforestry on an AmazonianFerralsolrdquo Experimental Agriculture vol 38 no 3 pp 277ndash2892002
[3] A R R Bastos J G Carvalho R P Assis and A B C FilholdquoMarcha de absorcao de nutrientes em urucum ( Bixa orellanaL) tipo cultivado piave vermelha em fase de viveirordquoCerne vol5 pp 76ndash85 1999
The Scientific World Journal 9
[4] E PThomasM Colvin S B Rosen C Zuccarini and S PetzerldquoHIV prevalence study and costing analysis undertaken for thedevelopment of an HIVAIDS workplace strategy for buffalocity municipalityrdquo Tech Rep Medical Research Council Buf-falo NY USA 2005
[5] C F Franco ldquoO Agronegocio do urucum na regiao Nordesterdquo 1Reuniao Nacional da Cadeia Produtiva de Urucum CD-Rom2007
[6] A Giorgi P De Marinis G Granelli L M Chiesa and SPanseri ldquoSecondary metabolite profile antioxidant capacityand mosquito repellent activity of Bixa orellana from BrazilianAmazon regionrdquo Journal of Chemistry vol 2013 Article ID409826 10 pages 2013
[7] J S Silva M D Moura R A G Oliveira M F F Dinizand J M Barbosa-Filho ldquoNatural product inhibitors of ovarianneoplasiardquo Phytomedicine vol 10 no 2-3 pp 221ndash232 2003
[8] F C F Sousa C T V Melo C O M Cito et al ldquoPlantasmedicinais e seus constituintes bioativos uma revisao dabioatividade e potenciais benefıcios nos disturbios da ansiedadeem modelos animaisrdquo Revista Brasileira de Farmacognosia vol18 pp 642ndash654 2008
[9] L J Quintans Jr J R G S Almeida J T Lima et al ldquoPlantswith anticonvulsant propertiesmdasha reviewrdquo Revista Brasileira deFarmacognosia vol 18 pp 798ndash819 2008
[10] HD S Falcao J A Leite JM Barbosa-Filho et al ldquoGastric andduodenal antiulcer activity of alkaloids a reviewrdquoMolecules vol13 no 12 pp 3198ndash3223 2008
[11] H S Falcao I R Mariath M F F M Diniz L M Batista andJ M Barbosa-Filho ldquoPlants of the American continent withantiulcer activityrdquo Phytomedicine vol 15 no 1-2 pp 132ndash1462008
[12] I R Mariath H D S Falcao J M Barbosa-Filho et al ldquoPlantsof the American continent with antimalarial activityrdquo RevistaBrasileira de Farmacognosia vol 19 no 1 pp 158ndash192 2009
[13] J E R Hon P M Soares C L Melo et al ldquoAtividadefarmacologica da monocrotalina isolada de plantas do generoCrotalariardquo Revista Brasileira de Farmacognosia vol 20 pp453ndash458 2010
[14] R N Almeida D S Navarro and J M Barbosa-Filho ldquoPlantswith central analgesic activityrdquo Phytomedicine vol 8 no 4 pp310ndash322 2001
[15] N Z T Jesus H S Falcao I F Gomes et al ldquoTanninspeptic ulcers and related mechanismsrdquo International Journal ofMolecular Sciences vol 13 no 3 pp 3203ndash3228 2012
[16] L G Rocha J R G S Almeida R O Macedo and J MBarbosa-Filho ldquoA review of natural products with antileishma-nial activityrdquo Phytomedicine vol 12 no 6-7 pp 514ndash535 2005
[17] G R M Lima C A Montenegro C L F Almeida PF Athayde-Filho J M Barbosa-Filho and L M BatistaldquoDatabase survey of anti-inflammatory plants in South Amer-ica a reviewrdquo International Journal ofMolecular Sciences vol 12no 4 pp 2692ndash2749 2011
[18] K S De Lira Mota G E N Dias M E F Pinto et alldquoFlavonoids with gastroprotective activityrdquo Molecules vol 14no 3 pp 979ndash1012 2009
[19] A L Souto J F Tavares M S da Silva M F F M de Diniz P Fde Athayde-Filho and J M Barbosa Filho ldquoAnti-inflammatoryactivity of alkaloids an update from 2000 to 2010rdquo Moleculesvol 16 no 10 pp 8515ndash8534 2011
[20] F L Silva D C H Fischer J F Tavares M S Silva P Fde Athayde-Filho and J M Barbosa-Filho ldquoCompilation of
secondary metabolites from Bidens pilosa LrdquoMolecules vol 16no 2 pp 1070ndash1102 2011
[21] J R Filho H de Sousa Falcao L M Batista J M B Filho andM R Piuvezam ldquoEffects of plant extracts on HIV-1 proteaserdquoCurrent HIV Research vol 8 no 7 pp 531ndash544 2010
[22] JM Barbosa-Filho A A Alencar X P Nunes et al ldquoSources ofalpha- beta- gamma- delta- and epsilon-carotenes a twentiethcentury reviewrdquo Revista Brasileirta de Farmacogn vol 18 no 1pp 135ndash154 2008
[23] S N S Silva C L F Amaral and T N H Reboucas ldquoAdoptionof conservation practices on farm and selection of varieties byproducers of annatto in the city of Vitoria da Conquista-BArdquoRevista Brasileira de Agroecologica vol 5 pp 106ndash113 2010
[24] A L Bandoni M E Mendiondo R V D Rondina and J DCoussio ldquoSurvey of Argentine medicinal plants I Folklore andphytochemical screeningrdquo Lloydia vol 35 no 1ndash4 pp 69ndash801972
[25] G H Garcia R Campos R A de Torres et al ldquoAntiherpeticactivity of some Argentine medicinal plantsrdquo Fitoterapia vol61 no 6 pp 542ndash546 1990
[26] M G L Brandao T S M Grandi E M M Rocha D RSawyer and A U Krettli ldquoSurvey of medicinal plants used asantimalarials in the Amazonrdquo Journal of Ethnopharmacologyvol 36 no 2 pp 175ndash182 1992
[27] M P Correa Dicionario das Plantas Uteis do Brasil e dasExoticas Cultivadas vol 4 Ministerio da AgriculturaIBDF Riode Janeiro Brasil 1978
[28] G S Hirschmann and A R de Arias ldquoA survey of medicinalplants of minas gerais Brazilrdquo Journal of Ethnopharmacologyvol 29 no 2 pp 159ndash172 1990
[29] R Otero R Fonnegra S L Jimenez et al ldquoSnakebites andethnobotany in the northwest region of Colombia Part Itraditional use of plantsrdquo Journal of Ethnopharmacology vol 71no 3 pp 493ndash504 2000
[30] H Garcia-Barriga Flora Medicinal de Colombia vol 2 Univer-sidad Nacional Bogota Colombia 1975
[31] J T Roig y Mesa Plantas Medicinales Aromaticas o Venenosasde Cuba Ministerio de Agricultura Havana Cuba 1945
[32] A Caceres H Menendez E Mendez et al ldquoAntigonorrhoealactivity of plants used inGuatemala for the treatment of sexuallytransmitted diseasesrdquo Journal of Ethnopharmacology vol 48no 2 pp 85ndash88 1995
[33] J A Duke and R V Martinez Amazonian EthnobotanicalDictionary CRC Press Boca Raton Fla USA 1994
[34] V R Ramirez L J Mostacero A E Garcia et al VegetalesEmpleados enMedicina Tradicional Norperuana Banco Agrariodel Peru Universidad Nacional de Trujillo Trujillo Peru 1988
[35] R Villar J M Calleja C Morales and A Caceres ldquoScreeningof 17 Guatemalan medicinal plants for platelet antiaggregantactivityrdquo Phytotherapy Research vol 11 pp 441ndash445 1997
[36] L M Giron V Freire A Alonzo and A Caceres ldquoEthnob-otanical survey of the medicinal flora used by the Caribs ofGuatemalardquo Journal of Ethnopharmacology vol 34 no 2-3 pp173ndash187 1991
[37] D L Lentz ldquoMedicinal and other economic plants of the PayaofHondurasrdquo Economic Botany vol 47 no 4 pp 358ndash370 1993
[38] D L Lentz A M Clark C D Hufford et al ldquoAntimi-crobial properties of Honduran medicinal plantsrdquo Journal ofEthnopharmacology vol 63 no 3 pp 253ndash263 1998
[39] E Y Morrison and M E West ldquoThe effect of Bixa orellana(Annatto) on blood sugar levels in the anaesthetized dogrdquoWestIndian Medical Journal vol 34 no 1 pp 38ndash42 1985
10 The Scientific World Journal
[40] F G Coe and G J Anderson ldquoScreening of medicinal plantsused by the Garıfuna of eastern Nicaragua for bioactive com-poundsrdquo Journal of Ethnopharmacology vol 53 no 1 pp 29ndash501996
[41] B Barrett ldquoMedicinal plants of Nicaraguarsquos Atlantic CoastrdquoEconomic Botany vol 48 no 1 pp 8ndash20 1994
[42] G Schmeda-Hirschmann and A R de Arias ldquoA screeningmethod for natural products on triatomine bugsrdquo PhytotherapyResearch vol 6 no 2 pp 68ndash73 1992
[43] G E Simpson ldquoFolk medicine in Trinidadrdquo The Journal ofAmerican Folklore vol 75 no 298 pp 326ndash340 1962
[44] D Mahabir and M C Gulliford ldquoUse of medicinal plants fordiabetes in Trinidad and Tobagordquo Revista Panamericana deSalud Publica vol 1 no 3 pp 174ndash179 1997
[45] E S Ayensu ldquoMedicinal plants of theWest IndiesrdquoUnpublishedManuscript 1978
[46] A Z Mercadante A Steck D Rodriguez-Amaya H Pfanderand G Britton ldquoIsolation of methyl 91015840Z-APO-61015840-lycopenoatefrom Bixa Orellanardquo Phytochemistry vol 41 no 4 pp 1201ndash1203 1996
[47] E Angelucci H K Arima E A Kumagai and I AnnattoldquoPreliminary data of the chemical compositionrdquo Coletanea doInstituto de Tecnologia de Alimentos vol 11 pp 89ndash96 1980
[48] A S L Tirimanna ldquoStudy of the carotenoid pigments of Bixaorellana L Seeds by thin layer chromatographyrdquo MikrochimicaActa vol 76 no 1-2 pp 11ndash16 1981
[49] J M Barbosa-Filho R N Silva-Filho B F Lira et al ldquoTeor debixina em quatro variedades de Bixa orellana L cultivadas naParaıbardquo Revista Brasileira de Farmacognosia vol 7-8 pp 41ndash47 1998
[50] A Z Mercadante A Steck and H Pfander ldquoIsolation andstructure elucidation of minor carotenoids from annatto (Bixaorellana L) seedsrdquo Phytochemistry vol 46 no 8 pp 1379ndash13831997
[51] C Prentice-Hernandez and O Rusig ldquoAnnatto (Bixa orellanaL) extract obtained using ethyl alcohol as a solventrdquo Arquivosde Biologia e Tecnologia vol 35 pp 63ndash74 1992
[52] A Z Mercadante ldquoComposition of carotenoids from annattordquoACS Symposium Series vol 775 pp 92ndash101 2001
[53] M J Scotter L A Wilson G P Appleton and L CastleldquoAnalysis of Annatto (Bixa orellana) Food Coloring Formula-tions 1 Determination of Coloring Components and ColoredThermal Degradation Products by High-Performance LiquidChromatography with Photodiode Array Detectionrdquo Journal ofAgricultural and Food Chemistry vol 46 no 3 pp 1031ndash10381998
[54] A J Degnan J H von Elbe and R W Hartel ldquoExtraction ofannatto seed pigment by supercritical carbon dioxiderdquo Journalof Food Science vol 56 pp 1655ndash1659 1991
[55] A ZMercadante A Steck andH Pfander ldquoIsolation and iden-tification of new apocarotenoids from annatto (Bixa orellana)seedsrdquo Journal of Agricultural and Food Chemistry vol 45 no4 pp 1050ndash1054 1997
[56] S G Anderson M G Nair A Chandra and E MorrisonldquoSupercritical fluid carbon dioxide extraction of annatto seedsand quantification of trans-bixin by high pressure liquid chro-matographyrdquo Phytochemical Analysis vol 8 pp 247ndash249 1997
[57] J M Barbosa-Filho Bixa orellana Retrospectiva de usos pop-ulares atividades biologicas fitoquımica e emprego na fito-cosmetica no continente americano Simposio Brasileiro doUrucummdashSIMBRAU Joao Pessoa Brazil 2006
[58] J Revilla Plantas da Amazonia Oportunidades Economicas eSustentaveis Manaus Programa de Desenvolvimento Empre-sarial e Tecnologico 2nd edition 2001
[59] F Oliveira G Akisue and M K Akisue FarmacognosiaAtheneu Sao Paulo Brazil 1996
[60] J Alonso Tratado de Fitofarmacos y Nutraceuticos CorpusRosario Argentina 2004
[61] C O Franco E G Fabri M Barreiro Neto M H Manfiolli MN C Harder and N C Rucker Urucum Sistema de Producaopara o Brasil Emepa-Pb Apta Joao Pessoa Brazil 2008
[62] P A Venugopalan G A Giridhar and A G RavishankarldquoFood Ethanobotanical and diversified applications of Bixaorellana L a scope for its improvement through biotechnolog-ical mediationrdquo Indian Journal of Fundamental and Applied LifeSciences vol 1 pp 9ndash31 2011
[63] L Taylor Herbal Secrets of the Rainforest Sage Press RocklinCalif USA 2nd edition 2002
[64] J S Oliveira Caracterizacao Extracao e Purificacao por Cro-matografia de Compostos de Urucum (Bixa orellana L) [tesisdoctoral en Ingenierıa Quımic] Universidade Federal de SantaCatarina Florianopolis Brazil 2005
[65] A Z Mercadante A Steck and H Pfander ldquoThree minorcarotenoids from annatto (Bixa orellana) seedsrdquo Phytochem-istry vol 52 no 1 pp 135ndash139 1999
[66] V Galindo-Cuspinera M B Lubran and S A Rankin ldquoCom-parison of volatile compounds in water- and oil-soluble annatto(Bixa orellana L) extractsrdquo Journal of Agricultural and FoodChemistry vol 50 no 7 pp 2010ndash2015 2002
[67] R O Alves de Lima L Azevedo L R Ribeiro and D M FSalvadori ldquoStudy on the mutagenicity and antimutagenicity ofa natural food colour (annatto) in mouse bone marrow cellsrdquoFood and Chemical Toxicology vol 41 no 2 pp 189ndash192 2003
[68] L R P Lima T T Oliveira T J Nagem et al ldquoBixina norbixinae quercetina e seus efeitos no metabolismo lipıdico de coelhosrdquoBrazilian Journal of Veterinary Research andAnimal Science vol38 pp 196ndash200 2001
[69] J D Fontana S V Mendes D S Persike L F Peracetta andM Passos ldquoCarotenoides cores atraentes e acao biologicardquoBiotecnologia Ciencia amp Desenvolvimento vol 2 p 13 2000
[70] C A Penna M Radice G O Gutkind et al ldquoAntibacterial andantifungal activities of some Argentinean plantsrdquo Fitoterapiavol 65 no 2 pp 172ndash174 1994
[71] A M Broussalis G E Ferraro V S Martino R Pinzon J DCoussio and J C Alvarez ldquoArgentine plants as potential sourceof insecticidal compoundsrdquo Journal of Ethnopharmacology vol67 no 2 pp 219ndash223 1999
[72] A Rojas de Arias G Schmeda-Hirschmann and A FalcaoldquoFeeding deterrency and insecticidal effects of plant extracts onLutzomyia longipalpisrdquo Phytotherapy Research vol 6 no 2 pp64ndash67 1992
[73] M S Pinheiro and M Z Rouquayrol ldquoMolluscicidal activityof plants from Northeast Brazilrdquo Revista Brasileira de PesquisasMedicas e Biologicas vol 7 pp 389ndash394 1974
[74] A Hagiwara N Imai T Ichihara et al ldquoA thirteen-week oraltoxicity study of annatto extract (norbixin) a natural food colorextracted from the seed coat of annatto (Bixa orellana L) inSprague-Dawley ratsrdquoFood andChemical Toxicology vol 41 no8 pp 1157ndash1164 2003
[75] C R Almeida R B Silva M J Marques and J K ChavascoldquoEvaluation of antiparasitic activity of hydroethanolic extractsfrom root stem and leaf of Bixa orellana L on Leishmania
The Scientific World Journal 11
amazonensis samplesrdquo Revista da Universidade Vale do RioVerde vol 10 no 2 pp 384ndash391 2012
[76] M V Lopes V C Desoti A D O Caleare T Ueda-NakamuraS O Silva and C V Nakamura ldquoMitochondria superoxideanion production contributes to geranylgeraniol-induced deathin leishmania amazonensisrdquo Evidence-Based Complementaryand Alternative Medicine vol 2012 Article ID 298320 9 pages2012
[77] J M Ferreira D F Sousa M B Dantas et al ldquoEffects of BixaorellanaL seeds onhyperlipidemiardquoPhytotherapyResearch vol27 no 1 pp 144ndash147 2013
[78] P S BenoitHH S FongGH Svoboda andN R FarnsworthldquoBiological and phytochemical evaluation of plants XIV Anti-inflammatory evaluation of 163 species of plantsrdquo Lloydia vol39 no 2-3 pp 160ndash171 1976
[79] D Carabajal A Casaco L Arruzazabala R Gonzalez andV Fuentes ldquoPharmacological screening of plant decoctionscommonly used in Cuban folk medicinerdquo Journal of Ethnophar-macology vol 33 no 1-2 pp 21ndash24 1991
[80] A F C Valdes J M Martınez D A Rodrıguez R S Lizamaand Y G Gaiten ldquoActividad antimalarica de un extractohidroalcoholico de Bixa orellanaLrdquo Revista Cubana de Medic-ina Tropical vol 63 pp 181ndash185 2011
[81] A D Garcıa H R Sanchez and R S Lizama ldquoCitotoxicidadde extractos de plantas medicinales sobre la lınea celularde carcinoma de pulmon humano A549rdquo Revista Cubana deFarmacia vol 45 pp 101ndash108 2011
[82] B Freixa R Vila L Vargas N Lozano T Adzet and SCanigueral ldquoScreening for antifungal activity of nineteen LatinAmerican plantsrdquo Phytotherapy Research vol 12 no 6 pp 427ndash430 1998
[83] A Caceres B Lopez S Gonzalez I Berger I Tada and JMaki ldquoPlants used in Guatemala for the treatment of pro-tozoal infections I Screening of activity to bacteria fungiand American trypanosomes of 13 native plantsrdquo Journal ofEthnopharmacology vol 62 no 3 pp 195ndash202 1998
[84] A Caceres O Cano B Samayoa and L Aguilar ldquoPlants usedin Guatemala for the treatment of gastrointestinal disorders1 Screening of 84 plants against enterobacteriardquo Journal ofEthnopharmacology vol 30 no 1 pp 55ndash73 1990
[85] A S Matsui S Hoskin M Kashiwagi et al ldquoA survey ofnatural products from Hawaii and other areas of the Pacificfor an antifertility effect in micerdquo Internationale Zeitschrift furKlinische PharmakologieTherapie und Toxikologie vol 5 no 1pp 65ndash69 1971
[86] M Abayomi A S Adebayo D Bennett R Porter and JS Campbell ldquoIn vitro antioxidant activity of Bixa orellana(Annatto) seed extractrdquo Journal of Applied PharmaceuticalScience vol 4 no 2 pp 101ndash106 2014
[87] NW Dunham and K R Allard ldquoA preliminary pharmacologicinvestigation of the roots of Bixa orellanardquo Journal of theAmerican Pharmacist Associantion vol 49 pp 218ndash219 1960
[88] F RMedina andRWoodbury ldquoTerrestrial plantsmolluscicidalto lymnaeid hosts of Fasciliasis hepatica in Puerto Ricordquo Journalof Agricultura of the University of Puerto Rico vol 63 pp 366ndash376 1979
[89] B Weniger Y Jiang A Oulad-Ali L Italiano J P Beck and RAnton ldquoBiological effects of bixin and Bixa orellana extracts onlymphoid cells in culturerdquo Planta Medica vol 59 no 7 articleA680 1993
[90] CM Chariandy C E Seaforth R H Phelps G V Pollard andB P S Khambay ldquoScreening of medicinal plants from Trinidad
and Tobago for antimicrobial and insecticidal propertiesrdquoJournal of Ethnopharmacology vol 64 no 3 pp 265ndash270 1999
[91] F J R Paumgartten R R Carvalho I B Araujo et alldquoEvaluation of the developmental toxicity of annatto in the ratrdquoFood and Chemical Toxicology vol 40 no 11 pp 1595ndash16012002
[92] C F Spencer F R Koniuszy E F Rogers et al ldquoSurvey of plantsfor antimalarial activityrdquo Lloydia vol 10 no 3 pp 145ndash174 1947
[93] H Mikkelsen J C Larsen and F Tarding ldquoHypersensitivityreactions to food colours with special reference to the naturalcolour annatto extract (butter colour)rdquo Toxicological Aspects ofFood Safety vol 1 pp 141ndash143 1978
Submit your manuscripts athttpwwwhindawicom
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Autoimmune Diseases
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Pharmaceutics
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MEDIATORSINFLAMMATION
of
2 The Scientific World Journal
bioactive molecules from various species of different plantfamilies [7ndash22] we offer this compilation of the traditionaluses chemical constituents and biological activities of Bixaorellana
The aim of this review is to highlight the biologicaland phytochemical studies that have been published aboutBixa orellana in South and Central America and try tocorrelate these studies with the popular uses of this plantin those regions as well as to evaluate whether its chemicalcomposition can support the reported biomedical propertiesrelated to Bixa orellana
2 Materials and Methods
In this work the biological activities and compounds isolatedfrom Bixa orellana were searched using the database ofthe Web of Science Scielo and the University of Illinoisin Chicago NAPRALERT (acronym for ldquoNAturalPRoductsALERTrdquo) The data were updated in April 2014 using ldquoBixaorellana chemical and bixinrdquo as keywords for this reviewThereferences found in the survey were later consulted for detailsabout the models or mechanisms of bioassays used to test theextracts of Bixa orellana
3 Botanical
The annatto tree belongs to the family Bixaceae and thegenus Bixa Despite the existence of several species the mostcommon in our country is Bixa orellana L named afterFrancisco Orellana who was the first European to navigatethe Amazon [23]
According to Revilla [58] B orellana is a small tree orshrub measuring from 3 to 5 meters in height sometimesreaching a height of 10 meters The trunk is short measuring20ndash30 cm in diameter with dark gray bark with lenticels invertical rows The leaves are alternate 10 to 20 cm long and 5to 10 cm wide sharp green on both sides and with extendedpetioles
According to Oliveira et al [59] seeds measure 03ndash05cm in length and 02-03 cm in diameter and their shapevaries frompyramidal to almost conicalThe number of seedsper capsule varies according to the author Alonso [60] foundthat each bivalvar capsule may contain from 30 to 60 seedson average
The seeds are considered the plant part of commercialimportance since the pericarp (layer that surrounds theseeds) contains the pigments that have wide industrial appli-cation About 80 of this pigment is the carotenoid known asbixin which has the dye property and can be extracted withvegetable oils or chemical bases Depending on the cultivarand climatic conditions of the region the bixin content canvary from 1 to 6 in the seed arilThe remainder is composedof other dyes and inert substances of minor importance [61]
4 Use in Traditional Medicine
Annatto is a native plant from South America more specif-ically of the Amazon region The popular name ldquourucumrdquo
comes from the Tupi word ldquoru-kurdquo which means ldquoredrdquo InBrazil this plant is commonly known as urucum urucuacafrao acafroa and acafroeira-da-terra It is known by otherpopular names in other countries atole achiote and bija(Peru and Cuba) axiote (Mexico) achiote achote anattobija and santo-domingo (Puerto Rico) bixa (Guyana) analto(Honduras) guajachote (El Salvador) onotto and onotillo(Venezuela) achiote and urucu (Bolivia) urucu (Argentina)roucou (Trinidad) roucou and koessewee (Suriname) andannatto (United States) The wide dissemination of its usein those regions is related to the growing demand fornatural dyes by many pharmaceutical cosmetic textile andespecially food industries [57]
According to Correa [27] seeds urucum supplies seedsthat have been used as a condiment as well as laxativecardiotonic hypotensive expectorant and antibiotic Inaddition it has anti-inflammatory activity for bruises andwounds and has been used for the treatment of bronchitis andfor wound healing purposes Oil is also obtained from thisplantThe infusion of the leaves has been shown to be effectiveagainst bronchitis sore throat and eye inflammation Thepulp which includes the seed is used for soft drinks andfebrifuge Moreover it can provide valuable dyeing materialssuch as yellow (orellin) and red (bixin) substances with thelatter constituting a crystallized active ingredient
In the food industry it is used to color butter margarinemayonnaise sauces mustard sausage soup juice ice creambakery productsmacaroni and cheese where it is commonlycalled ldquodo reinordquo (of the kingdom) coming from HollandIt is also widely used in the printing industry and dyemanufacturing Many Aborigines use annatto for dyeingwhere the dye is naturally obtained as a mixture and used tocolor ceramics and other vases for domestic use In additionmost endogenous people use this dye on their skin to beautifythemselves during religious rituals and mainly to protectthemselves from ultraviolet radiation and from mosquitoesthat infest forests [49] The bast provides fibers for roughcordage and the powder resulting from grinding the seedshas been used as an aphrodisiac Finally the infusion of coldbuds serves to wash inflamed eyes whereas the decoctionof the leaves has been used for antiemetic therapy duringpregnancy [27] (Table 1)
Thus despite the different culture and traditions amongthe countries in South and Central America several ofthe popular uses of Bixa orellana are the same for exam-ple antipyretic aphrodisiac antidiarrheal antidiabetic andinsect repellent
5 Chemical Compounds
Bixin a red-colored carotenoid is the pigment present inhigh concentration in the annatto seed aril It is the mainsubstance responsible for the dyeing characteristics of seedswhere its concentration can be as high as 50 Howeverdifferent seeds may have levels less than 20 and becausetheir commercial value is based on the bixin percentage levelshigher than 25 are usually required for export [61]
The Scientific World Journal 3
Table 1 Traditional uses of annatto in American countries
Countryuse Plant part ReferencesArgentina
Antipyreticcardiotonicantidiarrheal Seeds [24]Antidiarrhealdyescondiment Seeds [25]
BrazilBody paint Seeds [26]Insect repellent Seeds [27]Condimentfood coloring Seeds [27]Antipyretic Seeds [26]Antipyreticlaxativesburns Seeds [28]Malaria Seeds [26]
ColombiaSnakebite Leaves [29]Aphrodisiac Seeds [30]
CubaAphrodisiac Seeds [31]
GuatemalaGonorrheadysentery Leaves [32]Hepatitis Leaves [33]Dysentery Leaves [34]Blood diseases Leaves [35]Gonorrhea Roots [32]Diabetes Roots [36]
HondurasAromaticfood coloring Seeds [37]Paindigestivedysentery Leaves [38]
JamaicaDiabetes Seeds [39]
NicaraguaRespiratory and pulmonary disordersdiarrheadiureticburns Leaves + seeds [40]Labor pains Seeds [41]Coughcolddiureticdiarrheaburnslabor pains Seeds [40]
ParaguayInsecticiderepellent Seeds [42]Diabetes Seeds [39]
PeruAphrodisiacaphrodisiacdiureticantidisenteriaastringent Fruits [34]Antipyreticskin problems Leaves [33]Alcoholic hepatitisworms Roots [33]Antipyreticaphrodisiacdysenteryastringentstomach Seeds [34]
Trinidad and TobagoDiuretic Leaves [43]Diabetes Roots [44]Diabetes Roots [45]
Bixin was isolated for the first time from the seeds of Bixaorellana in 1875 and in 1961 its complete chemical structureand stereochemistry were determined by 1H and 13C-NMRBixin belongs to the small class of natural apocarotenoidswhose formation occurs by the oxidative degradation of C40carotenoids (Table 2)
Bixin consists of a chain of 25 carbons and has the molec-ular formula C
25H30O4(MW = 39451) It has a carboxylic
acid and methyl ester group at the ends of the chain Bixinoccurs in nature as 16-119885 (119888119894119904) but during the extractionprocess it isomerizes resulting in the 16-119864 form (trans) whichis called isobixin (Figure 1)
4 The Scientific World Journal
Table 2 The main carotenoids from the seeds of Bixa orellana
Carotenoid Country of isolation Physical aspect ReferencesApo-120595-carotene 91015840Z-61015840-ol Brazil Oil [46]
Beta carotene Brazil 183∘C [47]Suriname lowast [48]
Bixin
Brazil 198∘C [49ndash51]Peru lowast [52]
Dominican Rep lowast [53]Suriname lowast [48]USA lowast [54]
Z-Carotene Brazil Oil [46]Cryptoxanthin Suriname 173∘C [48]Dimethyl-(9Z)-661015840-diapocarotene-661015840-dioate Brazil Oil [52]Dimethyl-(9Z91015840Z)-661015840-diapocarotene-661015840-dioate Brazil Oil [50]Phytoene Brazil Oil [46]Phytofluene Brazil Oil [46]Geranylgeraniol Brazil Oil [52]Lutein Suriname 196∘C [48]Methyl-(9Z)-101015840-oxo-6101015840-diapocarotene-6-oate Brazil Oil [50]Methyl-(9Z)-61015840-oxo-651015840-diapocarotene-6-oate Brazil Oil [50]Methyl-(9Z)-81015840-oxo-681015840-diapocarotene-6-oate Brazil Oil [50]Methyl-(91015840Z)-apo-61015840-lycopenoate Brazil Oil [46]Methyl-(7Z9Z91015840Z)-apo-61015840-lycopenoate Brazil Oil [55]Methyl-(9Z)-apo-81015840-lycopenoate Brazil Oil [46]Methyl-(all-E)-apo-81015840-lycopenoate Brazil Oil [46]Neurosporene Brazil Oil [46]Norbixin Brazil 300∘C [52]Trans-bixin Jamaica 195∘C [56]Zeaxanthin Suriname 215∘C [48]Source [57]
Many other carotenoids (C19 C22 C24 C25 C30 and C
32)
occur in Bixa orellana but constitute a minor percentage ofthe pigments The major oily constituent of annatto seedsis geranylgeraniol representing 1 of dry seeds Norbixin(Figure 1) is a demethylated derivative of bixin and althoughit is a naturally occurring compound it is almost alwaysreferred to as a saponification product of bixin This is theform used for commercial purposes [62]
Currently more than two dozen substances have beenisolated from the seeds of Bixa orellana Besides bixin andnorbixin other compounds such as isobixin beta-carotenecryptoxanthin lutein zeaxanthin orellin bixein bixol cro-cetin ishwarane ellagic acid salicylic acid threonine tomen-tosic acid tryptophan and phenylalanine have been found inthe seeds of annatto In addition the following compounds intheir respective concentrations are found in these seeds 40to 45 cellulose 35 to 55 sugars 03 to 09 essential oils3 fixed oils 10 to 45 pigments and 13 to 16 proteinsand alpha and beta-carotene as well as tannins and saponins[63 64]
Mercadante et al [50 65] isolated eight apocarotenoidsfromannatto seedsmethyl (7Z 9Z 91015840Z)-apo-61015840-lycopenoatemethyl (9Z)-apo-81015840-lycopenoate methyl 1(all-E)-apo-81015840-lycopenoate methyl (all-E)-8-apo-beta-carotene-81015840-oate
methyl (all-E)-apo-61015840-lycopenoate 6-geranylgeranyl-81015840-methyl-681015840diapocaroten-6-81015840dioate 61015840-geranylgeranyl-61015840-methyl-(9Z)-661015840-diapocaroten-6-61015840-dioate and 6-geranylgeranyl-61015840-methyl-6-61015840-diapocaroten-6-61015840-dioate
More than 100 volatile compounds have been detectedin aqueous and organic extracts where 50 of these havealready been identified (eg bornyl acetateprop-caryophyllenecopaene prop-cubebene (+)-cyclosativene geranyl phenylac-etate 1-heptanetiol 3-methylpyridine 4-methylpyridine 120574-elemene 120573-humulene isoledene 120573-pinene seline-6-en-4-ol120575-selinene (minus)-spathulenol and (+)-ylangene) [66]
Because annatto is a rich source of carotenoids it isof great commercial importance In fact the therapeuticproperties of annatto (eg antioxidant and hypoglycemic)have been attributed to its high levels of carotenoids [67ndash69]Table 2 lists some of these compounds
The pigments in annatto seeds can be extracted bymechanical processes through grinding the seeds and byphysical-chemical methods using solvents or enzymes [46]The solvent extraction can be performed using three basicmethods alkaline extraction (NaOH or KOH solutions)which results in the conversion of bixin to norbixinextraction with oil (soybean corn) and extraction usingorganic solvents (hexane chloroform ethanol acetone or
The Scientific World Journal 5
Bixin (Z-bixin or cis-bixin)
COOH
COOMe
116
(a)
MeOOC 16 1
Isobixin (E-bixin or trans-bixin)
COOH
(b)
COOHHOOC
Norbixin
(c)
OH
Geranylgeraniol
(d)
Figure 1 Chemical structure of some pigments of annatto
propylene glycol) which results in the purest form of pig-ments
Barbosa-Filho et al [49] studied the seeds of four typesof annatto cultivated in Paraıba State Brazil namely ldquocas-caverderdquo (ldquogreen peelrdquo) ldquocascavermelhardquo (ldquored barkrdquo) ldquobicode calangordquo (ldquolizard beakrdquo) and ldquograopretordquo(ldquoblack grainrdquo)with respect to their oil (material extracted with hexane)and solid (material extracted with chloroform) contentsand also pure bixin which was obtained by successiverecrystallization from the chloroform fraction Pure bixinappears as red-purple crystals with a melting point of 196ndash198∘CThe different concentrations found for the oil fractionchloroform extract and bixin are as follows red bark 58lizard beak 51 green peel 49 and black grain 46 Redbark shows the highest yield for both solvent fractions andthe bixin amount is around 1This species has been reportedas the most used in folk medicine On the other hand blackgrain shows negligible amounts of bixin
6 Biological Activity
Table 3 shows data found in 38 studies performed withannatto in 15 different countries in the American countriesTo obtain the extracts and fractions tested several plant partswere used such as leaf root seed shoot and even the wholeplant The data surveyed were classified according to thepharmacological activity tested
Among the twenty-one activities tested those with thelargest number of studies performed were antifungal activity(12) antibacterial activity (12) antimalarial activity (6) andmutagenic activity (3) Cytotoxic activity and toxicity havebeen little studied with three and two studies respectivelyPharmacological activities have been evaluated in animalmodels (22 preclinical studies) human models (1 clinicalstudy) cell cultures (2 studies) and in vitro tests (32 studies)
Antifungal activity has been investigated in one countryin Central America (Guatemala) and in two countries inSouth America (Ecuador and Argentina) using eleven differ-ent fungal strains [70 82 84]
Freixa et al [82] conducted a study in Ecuador to assessthe antifungal activity of extracts from the dried leaves of
the annatto tree in response to 7 fungi species obtainingsatisfactory antifungal activity against Trichophyton menta-grophytes trains In Guatemala three different strains wereused to evaluate antifungal activity with no satisfactoryactivity being observed [84]
The extracts of annatto leaves have been evaluated forantibacterial activity against 8 different bacterial strains(Bacillus subtilis Escherichia coli Micrococcus luteus Pseu-domonas aeruginosa Staphylococcus aureus Salmonella typhiShigella dysenteriae and Staphylococcus epidermidis) show-ing no activity
Antimalarial activity has been determined against Plas-modium gallinaceum Plasmodium lophurae andPlasmodiumberghei Although the studies conducted previously in theUnited States did not show significant results [92] Valdes etal (2011) reported a moderate activity of the seed extracts ofBixa orellana against Plasmodium berghei and falciparum
7 Mutagenic and Cytotoxic Activities
No significant effect was observed when extracts of annattoseeds were tested for mutagenic activity in studies performedin the United States and Brazil [67 93]
Extracts obtained from annatto seeds and leaves havebeen tested in cell cultures and the brine shrimp assayrespectively and have been found to lack cytotoxicity ineither model used These experiments were carried out inGuatemala and the Dominican Republic [83 89]
On the other hand a study performed in Cuba with 10medicinal plants that were active in inhibiting human lungcarcinoma cell growth showed that the ethanolic extract ofBixa orellana presented cytotoxicity at concentrations below100 120583gmL [81]
8 Toxicological Activities
Currently concerns about the effect of synthetic dyes onhuman health are incontestable making people increasinglychoose those of natural origin believing that they are devoidof toxic effects This is not entirely true because even amedication from a natural source can be a poison depending
6 The Scientific World Journal
Table3Biologicalactiv
ities
ofextractsof
annatto
inAmerican
coun
tries
Cou
ntry
biologicalactiv
ityPartused
Type
ofextract
Organism
teste
dMod
elteste
dDoseu
sed
Activ
ityRe
ferences
Argentin
aAntibacteria
lLE
EtOH
Bacillussubtilis
Invitro
5mgmL
Inactiv
e[70]
Escherich
iacoli
Invitro
5mgmL
Inactiv
e[70]
Micrococcusluteus
Invitro
5mgmL
Inactiv
e[70]
Pseudomonas
aeruginosa
Invitro
5mgmL
Inactiv
e[70]
Staphylococcus
aureus
Invitro
5mgmL
Inactiv
e[70]
Antifu
ngal
LEEtOH
Aspergillus
niger
Invitro
5mgmL
Inactiv
e[70]
Cand
idaalbicans
Invitro
5mgmL
Inactiv
e[70]
Antivira
lSE
EtOH
VirusH
erpessim
plex
1Cell
cultu
re078
mgmL
Inactiv
e[71]
Insecticidal
AP
MeO
HInsect
Sitophilu
soryzae
5Inactiv
e[71]
Brazil
Antim
alarial
SECH
Cl3
Mou
sePlasmodium
berghei
100m
gkg
Inactiv
e[26]
Antioxidant
SEEtOH
Invitro
DPP
Hassay
01g
Lminus1
Activ
e[6]
Insectrepellent
SEPetr
eth
Ham
ster
Lutzom
yialongipalpis
1gL
Activ
e[72]
SEEtOH
Mosqu
itoAe
desa
egypti
182mgmL
Activ
e[6]
Molluscicidal
SEEtOH
Con
chBiom
phalariagla
brata
10000
ppm
Inactiv
e[73]
Mutagenic
Powder
Mou
seBo
nemarrowcells
10670
ppm
Inactiv
e[67]
Toxicity
SEPo
wder
Rat
Invivo
500m
gkg
Inactiv
e[74]
Antileish
manial
LERO
EtOH
Leish
maniaam
azonensis
Invitro
012ndash25mgmL
Activ
e[75]
Antileish
manial
SEOE
Leish
maniaam
azonensis
Invitro
10501005001000120583gmL
Activ
e[76]
Hyperlip
idem
iaSE
H2O
Mou
seIn
vitro
400and800m
gkg
Activ
e[77]
Colom
bia
Snakebite
LEEtOH
Mou
seBo
throps
atrox
LD50gt260120583
ganim
alAc
tive
[29]
CostaRica
Anti-infl
ammatory
ROEtOH
Rat
Pawedem
acarrageenan
100m
gkg
Inactiv
e[78]
Cuba Positiveino
tropice
ffect
AP
H2O
Guineap
igIsolated
atriu
m320120583
LInactiv
e[79]
Antim
alarial
SEPlasmodium
gallina
ceum
falciparum
Invivoin
vitro
500m
gkg
Activ
e[80]
Cytotoxic
SEEtOH
Tumor
cells
Invitro
39ndash
250m
gmL
Activ
e[81]
Ecuado
rAntifu
ngal
LEMeO
HAspergillus
niger
Invitro
10mgdisk
Inactiv
e[82]
Cand
idaalbicans
Invitro
10mgdisk
Inactiv
e[82]
Cryptococcus
neoforman
sIn
vitro
10mgdisk
Inactiv
e[82]
Fusariu
moxysporum
Invitro
10mgdisk
Inactiv
e[82]
Neurospora
crassa
Invitro
10mgdisk
Inactiv
e[82]
Penicilliu
mpurpurogenum
Invitro
10mgdisk
Inactiv
e[82]
Trich
ophytonmentagrophytes
Invitro
10mgdisk
Activ
e[82]
The Scientific World Journal 7
Table3Con
tinued
Cou
ntry
biologicalactiv
ityPartused
Type
ofextract
Organism
teste
dMod
elteste
dDoseu
sed
Activ
ityRe
ferences
Guatemala
Antibacteria
lLE
Vario
usEscherich
iacoli
Invitro
50120583Ldisk
Inactiv
e[83]
Pseudomonas
aeruginosa
Invitro
MICgt10mgmL
Inactiv
e[83]
Salm
onellatyphi
Invitro
MICgt10mgmL
Inactiv
e[83]
Shigelladysenteriae
Invitro
50120583L
Inactiv
e[83]
Staphylococcus
aureus
Invitro
MICgt10mgmL
Inactiv
e[83]
Antifu
ngal
LEH
2OAspergillus
flavus
Invitro
MICgt10mgmL
Inactiv
e[84]
Cand
idaalbicans
Invitro
MICgt10mgmL
Inactiv
e[84]
Microsporum
gypseum
Invitro
MICgt10mgmL
Inactiv
e[84]
Antigon
orrheal
LEEtOH
Neisseriagonorrhea
Invitro
50120583Ldisk
Activ
e[32]
Antitrypanosom
alLE
EtOH
Trypanosom
acruzi
Invitro
MICgt1m
gmL
Inactiv
e[83]
Cytotoxic
LEH
2OCr
ustacean
Artemiasalin
aLC
50gt10
00pp
mInactiv
e[83]
Inhibof
plateletaggregation
SE
Invitro
Thrombinaggregation
IC50
0795m
gmL
Inactiv
e[35]
Haw
aii
Con
traceptiv
eRO
Mou
se
02m
Lanim
alInactiv
e[85]
Jamaica
Hypoglycemic
SECH
Cl3
Dog
1gAc
tive
[39]
H2O
Dog
200m
Lanim
alAc
tive
[39]
Antioxidant
SEEtOH
Invitro
Invitro
025
and25120583
gmL
Activ
e[86]
Mexico
Allergenic
SEOil
Hum
an25120583L
person
Activ
e[87]
Paragu
ayInsecticidal
SEPetr
ether
Insect
Rhodnius
negle
ctus
50120583g
Inactiv
e[42]
Puerto
Rico
Molluscicidal
TPH
2OCon
chLymna
eacubensis
LD100gt1M
ppm
Inactiv
e[88]
Dom
inican
Repu
blic
Cytotoxic
SEEtOH
Cellculture
Molt4
cells
200120583
gmL
Inactiv
e[89]
Trinidad
andTo
bago
Antibacteria
lSE
EtOAc
Escherich
iacoli
Invitro
1000120583gmL
Inactiv
e[90]
Pseudomonas
aeruginosa
Invitro
1000120583gmL
Inactiv
e[90]
USA A
nticon
vulsa
ntRA
EtOH
Mou
seSeizureselectroshock
100m
gkg
Inactiv
e[91]
Rat
Seizurespentylenetetrazole
400m
gkg
Inactiv
e[91]
Antim
alarial
SECH
Cl3
Chicken
Plasmodium
gallina
ceum
388m
gkg
Inactiv
e[92]
Mutagenic
SEMeO
HSalm
onellatyphim
urium
100m
gplaque
Inactiv
e[93]
H2O
Invitro
Placentaltroph
oblasts
100m
gplaque
Inactiv
e[93]
Hypotensiv
eRA
EtOH
Rat
50mgkg
Activ
e[93]
Toxicity
RAH
2OMou
seLD
50gt700m
gkg
Inactiv
e[92]
LEleafAP
aeria
lpartTP
totalplantRO
roo
tSE
seedno
tgivenLD5050
lethaldo
seIC5
0concentrationthatinhibits50of
thee
ffectM
ICm
inim
uminhibitory
concentration
8 The Scientific World Journal
on the dose that is administered The failure to require in-depth data related to toxicological and chemical analysesfor the registration of food additives derived from naturalsources [67 74] certainly makes the information aboutpossible unwanted effects andor pharmacological activitiesresulting from their use much rarer than expected in view ofthe importance of the topic In Brazil the use of annatto is sowidespread that its safety is not even questioned
Paumgartten et al [91] evaluated the toxicity of annattoextracts in rats Doses up to 500mgkg body weightdaywere introduced directly into the stomach of pregnant ratsto evaluate the effect on the mother and fetus and noadverse effects were found for either The annatto extract didnot induce an increase in the incidence of visible externalvisceral or skeletal anomalies in the fetuses Therefore thestudy suggested that the annatto extract was not toxic to ratsnor was it embryotoxic Studies performed in Brazil by Alvesde Lima et al [67] where extracts of annatto weremixed withthe food of male rats showed that the concentrations testedhad no mutagenic or antimutagenic activity in their bonemarrow cells A parallel toxicity study conducted byHagiwaraet al [74] showed that 01 annatto extract administered forthirteen weeks in the feed of male and female rats did notshow any adverse effects However when higher doses wereadministered (03 and 09) the authors noticed an increasein liver weight as well as changes in blood chemistriesincluding increase in alkaline phosphatase phospholipidsand total protein as well as albumin and albuminglobulinratio
Hagiwara et al [74] also evaluated extracts of annattofor liver carcinogenicity in rats and found no evidence ofliver tumors even when given to animals at a high dose of200mgkg body weightday compared to an acceptable doseof 00 to 0065mgkgday thus indicating that the dangerof a hepatocarcinogenic effect in humans may be absent ornegligible
A toxicity test was performedwith extracts obtained fromboth plant seeds and shoots and no significant effect wasobserved The experiments were performed in the UnitedStates using mice as the animal model and it was found thatthe LD50 was greater than 700mgkg [92]
9 Correlation between the BiologicalActivities Phytochemistry and theTraditional Uses of Bixa orellana
Table 1 shows that many of the traditional uses of Bixaorellana are the same in several countries of South andCentral America which suggests its effectiveness as a ther-apeutic agent Extracts of Bixa orellana showed biologicalactivities such as antioxidant hypotensive molluscicideand antimalarial against A549 cells for carcinoma of thelung allergy hypoglycemic antifungal antioxidant insectrepellent antigonococcal and antivenom serum and some ofthem are in accordance with the traditional use for examplein Brazil it is used to extract the seeds with purpose repellentinsecticide and antimalaria and scientific studies in the samecountrywith the Lutzomyia longipalpis insect repellent action
and prove a study in Cuba proved the pharmacological actionfor antimalarial activity when tested against Plasmodiumberghei Some of them are in accordance with the traditionaluse for example seed extracts have been used in Brazil andCuba as insect repellent and antimalarial Antioxidant andinsect repellent activities can be attributed to the carotenoidsand the essential and fixed oils respectively
Despite the previous reports about the presence of com-ponents with anti-inflammatory properties such as salicylicacid lutein polyphenols and tannins this activity has not yetbeen proven for Bixa orellana extracts Similarly the plantrsquosessential and fixed oils have shown antibacterial propertiesalthough this activity has not been proven too
In general the data obtained in this review do not allowcorrelations between the biologic activities tested in vitro or invivo with the compounds identified in this species Howevertaking into account the related activities such as the antipara-sitic effect and the lack of mutagenic and cytotoxicity activityit is possible to consider Bixa orellana as a potential source forthe development of phytopharmaceutical products
In conclusion the studies discussed in this review repre-sent a rich database around the Bixa orellana activities andits potential uses which evokes the feasibility of phytophar-maceuticals to treat some diseases whenever an antioxidanthypotensor or hypoglycemiant activity is necessary
Although the commercial exploitation of this species iswell established there are very few studies on its pharma-cological effects Considering the need for developing a safeand effective product more studies should be performed inorder to confirm other biological activities supported by thepopular uses of Bixa orellana
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors are grateful to CNPqPRONEXFAPESQ andCAPES for financial support and to the NAPRALERTDatabase of the University of Illinois USA for the literatureon Bixa orellana A Leyva helped in editing the Englishlanguage of the paper
References
[1] M B Perecin O A Bovi and N B Maia ldquoPesquisa complantas aromaticas medicinais corantes o papel do InstitutoAgronomicordquo O Agronomico vol 54 pp 21ndash24 2002
[2] M E A Elias G Schroth J L V Macedo M S S Motaand S A DrsquoAngelo ldquoMineral nutrition growth and yields ofannatto trees (Bixa orellana) in agroforestry on an AmazonianFerralsolrdquo Experimental Agriculture vol 38 no 3 pp 277ndash2892002
[3] A R R Bastos J G Carvalho R P Assis and A B C FilholdquoMarcha de absorcao de nutrientes em urucum ( Bixa orellanaL) tipo cultivado piave vermelha em fase de viveirordquoCerne vol5 pp 76ndash85 1999
The Scientific World Journal 9
[4] E PThomasM Colvin S B Rosen C Zuccarini and S PetzerldquoHIV prevalence study and costing analysis undertaken for thedevelopment of an HIVAIDS workplace strategy for buffalocity municipalityrdquo Tech Rep Medical Research Council Buf-falo NY USA 2005
[5] C F Franco ldquoO Agronegocio do urucum na regiao Nordesterdquo 1Reuniao Nacional da Cadeia Produtiva de Urucum CD-Rom2007
[6] A Giorgi P De Marinis G Granelli L M Chiesa and SPanseri ldquoSecondary metabolite profile antioxidant capacityand mosquito repellent activity of Bixa orellana from BrazilianAmazon regionrdquo Journal of Chemistry vol 2013 Article ID409826 10 pages 2013
[7] J S Silva M D Moura R A G Oliveira M F F Dinizand J M Barbosa-Filho ldquoNatural product inhibitors of ovarianneoplasiardquo Phytomedicine vol 10 no 2-3 pp 221ndash232 2003
[8] F C F Sousa C T V Melo C O M Cito et al ldquoPlantasmedicinais e seus constituintes bioativos uma revisao dabioatividade e potenciais benefıcios nos disturbios da ansiedadeem modelos animaisrdquo Revista Brasileira de Farmacognosia vol18 pp 642ndash654 2008
[9] L J Quintans Jr J R G S Almeida J T Lima et al ldquoPlantswith anticonvulsant propertiesmdasha reviewrdquo Revista Brasileira deFarmacognosia vol 18 pp 798ndash819 2008
[10] HD S Falcao J A Leite JM Barbosa-Filho et al ldquoGastric andduodenal antiulcer activity of alkaloids a reviewrdquoMolecules vol13 no 12 pp 3198ndash3223 2008
[11] H S Falcao I R Mariath M F F M Diniz L M Batista andJ M Barbosa-Filho ldquoPlants of the American continent withantiulcer activityrdquo Phytomedicine vol 15 no 1-2 pp 132ndash1462008
[12] I R Mariath H D S Falcao J M Barbosa-Filho et al ldquoPlantsof the American continent with antimalarial activityrdquo RevistaBrasileira de Farmacognosia vol 19 no 1 pp 158ndash192 2009
[13] J E R Hon P M Soares C L Melo et al ldquoAtividadefarmacologica da monocrotalina isolada de plantas do generoCrotalariardquo Revista Brasileira de Farmacognosia vol 20 pp453ndash458 2010
[14] R N Almeida D S Navarro and J M Barbosa-Filho ldquoPlantswith central analgesic activityrdquo Phytomedicine vol 8 no 4 pp310ndash322 2001
[15] N Z T Jesus H S Falcao I F Gomes et al ldquoTanninspeptic ulcers and related mechanismsrdquo International Journal ofMolecular Sciences vol 13 no 3 pp 3203ndash3228 2012
[16] L G Rocha J R G S Almeida R O Macedo and J MBarbosa-Filho ldquoA review of natural products with antileishma-nial activityrdquo Phytomedicine vol 12 no 6-7 pp 514ndash535 2005
[17] G R M Lima C A Montenegro C L F Almeida PF Athayde-Filho J M Barbosa-Filho and L M BatistaldquoDatabase survey of anti-inflammatory plants in South Amer-ica a reviewrdquo International Journal ofMolecular Sciences vol 12no 4 pp 2692ndash2749 2011
[18] K S De Lira Mota G E N Dias M E F Pinto et alldquoFlavonoids with gastroprotective activityrdquo Molecules vol 14no 3 pp 979ndash1012 2009
[19] A L Souto J F Tavares M S da Silva M F F M de Diniz P Fde Athayde-Filho and J M Barbosa Filho ldquoAnti-inflammatoryactivity of alkaloids an update from 2000 to 2010rdquo Moleculesvol 16 no 10 pp 8515ndash8534 2011
[20] F L Silva D C H Fischer J F Tavares M S Silva P Fde Athayde-Filho and J M Barbosa-Filho ldquoCompilation of
secondary metabolites from Bidens pilosa LrdquoMolecules vol 16no 2 pp 1070ndash1102 2011
[21] J R Filho H de Sousa Falcao L M Batista J M B Filho andM R Piuvezam ldquoEffects of plant extracts on HIV-1 proteaserdquoCurrent HIV Research vol 8 no 7 pp 531ndash544 2010
[22] JM Barbosa-Filho A A Alencar X P Nunes et al ldquoSources ofalpha- beta- gamma- delta- and epsilon-carotenes a twentiethcentury reviewrdquo Revista Brasileirta de Farmacogn vol 18 no 1pp 135ndash154 2008
[23] S N S Silva C L F Amaral and T N H Reboucas ldquoAdoptionof conservation practices on farm and selection of varieties byproducers of annatto in the city of Vitoria da Conquista-BArdquoRevista Brasileira de Agroecologica vol 5 pp 106ndash113 2010
[24] A L Bandoni M E Mendiondo R V D Rondina and J DCoussio ldquoSurvey of Argentine medicinal plants I Folklore andphytochemical screeningrdquo Lloydia vol 35 no 1ndash4 pp 69ndash801972
[25] G H Garcia R Campos R A de Torres et al ldquoAntiherpeticactivity of some Argentine medicinal plantsrdquo Fitoterapia vol61 no 6 pp 542ndash546 1990
[26] M G L Brandao T S M Grandi E M M Rocha D RSawyer and A U Krettli ldquoSurvey of medicinal plants used asantimalarials in the Amazonrdquo Journal of Ethnopharmacologyvol 36 no 2 pp 175ndash182 1992
[27] M P Correa Dicionario das Plantas Uteis do Brasil e dasExoticas Cultivadas vol 4 Ministerio da AgriculturaIBDF Riode Janeiro Brasil 1978
[28] G S Hirschmann and A R de Arias ldquoA survey of medicinalplants of minas gerais Brazilrdquo Journal of Ethnopharmacologyvol 29 no 2 pp 159ndash172 1990
[29] R Otero R Fonnegra S L Jimenez et al ldquoSnakebites andethnobotany in the northwest region of Colombia Part Itraditional use of plantsrdquo Journal of Ethnopharmacology vol 71no 3 pp 493ndash504 2000
[30] H Garcia-Barriga Flora Medicinal de Colombia vol 2 Univer-sidad Nacional Bogota Colombia 1975
[31] J T Roig y Mesa Plantas Medicinales Aromaticas o Venenosasde Cuba Ministerio de Agricultura Havana Cuba 1945
[32] A Caceres H Menendez E Mendez et al ldquoAntigonorrhoealactivity of plants used inGuatemala for the treatment of sexuallytransmitted diseasesrdquo Journal of Ethnopharmacology vol 48no 2 pp 85ndash88 1995
[33] J A Duke and R V Martinez Amazonian EthnobotanicalDictionary CRC Press Boca Raton Fla USA 1994
[34] V R Ramirez L J Mostacero A E Garcia et al VegetalesEmpleados enMedicina Tradicional Norperuana Banco Agrariodel Peru Universidad Nacional de Trujillo Trujillo Peru 1988
[35] R Villar J M Calleja C Morales and A Caceres ldquoScreeningof 17 Guatemalan medicinal plants for platelet antiaggregantactivityrdquo Phytotherapy Research vol 11 pp 441ndash445 1997
[36] L M Giron V Freire A Alonzo and A Caceres ldquoEthnob-otanical survey of the medicinal flora used by the Caribs ofGuatemalardquo Journal of Ethnopharmacology vol 34 no 2-3 pp173ndash187 1991
[37] D L Lentz ldquoMedicinal and other economic plants of the PayaofHondurasrdquo Economic Botany vol 47 no 4 pp 358ndash370 1993
[38] D L Lentz A M Clark C D Hufford et al ldquoAntimi-crobial properties of Honduran medicinal plantsrdquo Journal ofEthnopharmacology vol 63 no 3 pp 253ndash263 1998
[39] E Y Morrison and M E West ldquoThe effect of Bixa orellana(Annatto) on blood sugar levels in the anaesthetized dogrdquoWestIndian Medical Journal vol 34 no 1 pp 38ndash42 1985
10 The Scientific World Journal
[40] F G Coe and G J Anderson ldquoScreening of medicinal plantsused by the Garıfuna of eastern Nicaragua for bioactive com-poundsrdquo Journal of Ethnopharmacology vol 53 no 1 pp 29ndash501996
[41] B Barrett ldquoMedicinal plants of Nicaraguarsquos Atlantic CoastrdquoEconomic Botany vol 48 no 1 pp 8ndash20 1994
[42] G Schmeda-Hirschmann and A R de Arias ldquoA screeningmethod for natural products on triatomine bugsrdquo PhytotherapyResearch vol 6 no 2 pp 68ndash73 1992
[43] G E Simpson ldquoFolk medicine in Trinidadrdquo The Journal ofAmerican Folklore vol 75 no 298 pp 326ndash340 1962
[44] D Mahabir and M C Gulliford ldquoUse of medicinal plants fordiabetes in Trinidad and Tobagordquo Revista Panamericana deSalud Publica vol 1 no 3 pp 174ndash179 1997
[45] E S Ayensu ldquoMedicinal plants of theWest IndiesrdquoUnpublishedManuscript 1978
[46] A Z Mercadante A Steck D Rodriguez-Amaya H Pfanderand G Britton ldquoIsolation of methyl 91015840Z-APO-61015840-lycopenoatefrom Bixa Orellanardquo Phytochemistry vol 41 no 4 pp 1201ndash1203 1996
[47] E Angelucci H K Arima E A Kumagai and I AnnattoldquoPreliminary data of the chemical compositionrdquo Coletanea doInstituto de Tecnologia de Alimentos vol 11 pp 89ndash96 1980
[48] A S L Tirimanna ldquoStudy of the carotenoid pigments of Bixaorellana L Seeds by thin layer chromatographyrdquo MikrochimicaActa vol 76 no 1-2 pp 11ndash16 1981
[49] J M Barbosa-Filho R N Silva-Filho B F Lira et al ldquoTeor debixina em quatro variedades de Bixa orellana L cultivadas naParaıbardquo Revista Brasileira de Farmacognosia vol 7-8 pp 41ndash47 1998
[50] A Z Mercadante A Steck and H Pfander ldquoIsolation andstructure elucidation of minor carotenoids from annatto (Bixaorellana L) seedsrdquo Phytochemistry vol 46 no 8 pp 1379ndash13831997
[51] C Prentice-Hernandez and O Rusig ldquoAnnatto (Bixa orellanaL) extract obtained using ethyl alcohol as a solventrdquo Arquivosde Biologia e Tecnologia vol 35 pp 63ndash74 1992
[52] A Z Mercadante ldquoComposition of carotenoids from annattordquoACS Symposium Series vol 775 pp 92ndash101 2001
[53] M J Scotter L A Wilson G P Appleton and L CastleldquoAnalysis of Annatto (Bixa orellana) Food Coloring Formula-tions 1 Determination of Coloring Components and ColoredThermal Degradation Products by High-Performance LiquidChromatography with Photodiode Array Detectionrdquo Journal ofAgricultural and Food Chemistry vol 46 no 3 pp 1031ndash10381998
[54] A J Degnan J H von Elbe and R W Hartel ldquoExtraction ofannatto seed pigment by supercritical carbon dioxiderdquo Journalof Food Science vol 56 pp 1655ndash1659 1991
[55] A ZMercadante A Steck andH Pfander ldquoIsolation and iden-tification of new apocarotenoids from annatto (Bixa orellana)seedsrdquo Journal of Agricultural and Food Chemistry vol 45 no4 pp 1050ndash1054 1997
[56] S G Anderson M G Nair A Chandra and E MorrisonldquoSupercritical fluid carbon dioxide extraction of annatto seedsand quantification of trans-bixin by high pressure liquid chro-matographyrdquo Phytochemical Analysis vol 8 pp 247ndash249 1997
[57] J M Barbosa-Filho Bixa orellana Retrospectiva de usos pop-ulares atividades biologicas fitoquımica e emprego na fito-cosmetica no continente americano Simposio Brasileiro doUrucummdashSIMBRAU Joao Pessoa Brazil 2006
[58] J Revilla Plantas da Amazonia Oportunidades Economicas eSustentaveis Manaus Programa de Desenvolvimento Empre-sarial e Tecnologico 2nd edition 2001
[59] F Oliveira G Akisue and M K Akisue FarmacognosiaAtheneu Sao Paulo Brazil 1996
[60] J Alonso Tratado de Fitofarmacos y Nutraceuticos CorpusRosario Argentina 2004
[61] C O Franco E G Fabri M Barreiro Neto M H Manfiolli MN C Harder and N C Rucker Urucum Sistema de Producaopara o Brasil Emepa-Pb Apta Joao Pessoa Brazil 2008
[62] P A Venugopalan G A Giridhar and A G RavishankarldquoFood Ethanobotanical and diversified applications of Bixaorellana L a scope for its improvement through biotechnolog-ical mediationrdquo Indian Journal of Fundamental and Applied LifeSciences vol 1 pp 9ndash31 2011
[63] L Taylor Herbal Secrets of the Rainforest Sage Press RocklinCalif USA 2nd edition 2002
[64] J S Oliveira Caracterizacao Extracao e Purificacao por Cro-matografia de Compostos de Urucum (Bixa orellana L) [tesisdoctoral en Ingenierıa Quımic] Universidade Federal de SantaCatarina Florianopolis Brazil 2005
[65] A Z Mercadante A Steck and H Pfander ldquoThree minorcarotenoids from annatto (Bixa orellana) seedsrdquo Phytochem-istry vol 52 no 1 pp 135ndash139 1999
[66] V Galindo-Cuspinera M B Lubran and S A Rankin ldquoCom-parison of volatile compounds in water- and oil-soluble annatto(Bixa orellana L) extractsrdquo Journal of Agricultural and FoodChemistry vol 50 no 7 pp 2010ndash2015 2002
[67] R O Alves de Lima L Azevedo L R Ribeiro and D M FSalvadori ldquoStudy on the mutagenicity and antimutagenicity ofa natural food colour (annatto) in mouse bone marrow cellsrdquoFood and Chemical Toxicology vol 41 no 2 pp 189ndash192 2003
[68] L R P Lima T T Oliveira T J Nagem et al ldquoBixina norbixinae quercetina e seus efeitos no metabolismo lipıdico de coelhosrdquoBrazilian Journal of Veterinary Research andAnimal Science vol38 pp 196ndash200 2001
[69] J D Fontana S V Mendes D S Persike L F Peracetta andM Passos ldquoCarotenoides cores atraentes e acao biologicardquoBiotecnologia Ciencia amp Desenvolvimento vol 2 p 13 2000
[70] C A Penna M Radice G O Gutkind et al ldquoAntibacterial andantifungal activities of some Argentinean plantsrdquo Fitoterapiavol 65 no 2 pp 172ndash174 1994
[71] A M Broussalis G E Ferraro V S Martino R Pinzon J DCoussio and J C Alvarez ldquoArgentine plants as potential sourceof insecticidal compoundsrdquo Journal of Ethnopharmacology vol67 no 2 pp 219ndash223 1999
[72] A Rojas de Arias G Schmeda-Hirschmann and A FalcaoldquoFeeding deterrency and insecticidal effects of plant extracts onLutzomyia longipalpisrdquo Phytotherapy Research vol 6 no 2 pp64ndash67 1992
[73] M S Pinheiro and M Z Rouquayrol ldquoMolluscicidal activityof plants from Northeast Brazilrdquo Revista Brasileira de PesquisasMedicas e Biologicas vol 7 pp 389ndash394 1974
[74] A Hagiwara N Imai T Ichihara et al ldquoA thirteen-week oraltoxicity study of annatto extract (norbixin) a natural food colorextracted from the seed coat of annatto (Bixa orellana L) inSprague-Dawley ratsrdquoFood andChemical Toxicology vol 41 no8 pp 1157ndash1164 2003
[75] C R Almeida R B Silva M J Marques and J K ChavascoldquoEvaluation of antiparasitic activity of hydroethanolic extractsfrom root stem and leaf of Bixa orellana L on Leishmania
The Scientific World Journal 11
amazonensis samplesrdquo Revista da Universidade Vale do RioVerde vol 10 no 2 pp 384ndash391 2012
[76] M V Lopes V C Desoti A D O Caleare T Ueda-NakamuraS O Silva and C V Nakamura ldquoMitochondria superoxideanion production contributes to geranylgeraniol-induced deathin leishmania amazonensisrdquo Evidence-Based Complementaryand Alternative Medicine vol 2012 Article ID 298320 9 pages2012
[77] J M Ferreira D F Sousa M B Dantas et al ldquoEffects of BixaorellanaL seeds onhyperlipidemiardquoPhytotherapyResearch vol27 no 1 pp 144ndash147 2013
[78] P S BenoitHH S FongGH Svoboda andN R FarnsworthldquoBiological and phytochemical evaluation of plants XIV Anti-inflammatory evaluation of 163 species of plantsrdquo Lloydia vol39 no 2-3 pp 160ndash171 1976
[79] D Carabajal A Casaco L Arruzazabala R Gonzalez andV Fuentes ldquoPharmacological screening of plant decoctionscommonly used in Cuban folk medicinerdquo Journal of Ethnophar-macology vol 33 no 1-2 pp 21ndash24 1991
[80] A F C Valdes J M Martınez D A Rodrıguez R S Lizamaand Y G Gaiten ldquoActividad antimalarica de un extractohidroalcoholico de Bixa orellanaLrdquo Revista Cubana de Medic-ina Tropical vol 63 pp 181ndash185 2011
[81] A D Garcıa H R Sanchez and R S Lizama ldquoCitotoxicidadde extractos de plantas medicinales sobre la lınea celularde carcinoma de pulmon humano A549rdquo Revista Cubana deFarmacia vol 45 pp 101ndash108 2011
[82] B Freixa R Vila L Vargas N Lozano T Adzet and SCanigueral ldquoScreening for antifungal activity of nineteen LatinAmerican plantsrdquo Phytotherapy Research vol 12 no 6 pp 427ndash430 1998
[83] A Caceres B Lopez S Gonzalez I Berger I Tada and JMaki ldquoPlants used in Guatemala for the treatment of pro-tozoal infections I Screening of activity to bacteria fungiand American trypanosomes of 13 native plantsrdquo Journal ofEthnopharmacology vol 62 no 3 pp 195ndash202 1998
[84] A Caceres O Cano B Samayoa and L Aguilar ldquoPlants usedin Guatemala for the treatment of gastrointestinal disorders1 Screening of 84 plants against enterobacteriardquo Journal ofEthnopharmacology vol 30 no 1 pp 55ndash73 1990
[85] A S Matsui S Hoskin M Kashiwagi et al ldquoA survey ofnatural products from Hawaii and other areas of the Pacificfor an antifertility effect in micerdquo Internationale Zeitschrift furKlinische PharmakologieTherapie und Toxikologie vol 5 no 1pp 65ndash69 1971
[86] M Abayomi A S Adebayo D Bennett R Porter and JS Campbell ldquoIn vitro antioxidant activity of Bixa orellana(Annatto) seed extractrdquo Journal of Applied PharmaceuticalScience vol 4 no 2 pp 101ndash106 2014
[87] NW Dunham and K R Allard ldquoA preliminary pharmacologicinvestigation of the roots of Bixa orellanardquo Journal of theAmerican Pharmacist Associantion vol 49 pp 218ndash219 1960
[88] F RMedina andRWoodbury ldquoTerrestrial plantsmolluscicidalto lymnaeid hosts of Fasciliasis hepatica in Puerto Ricordquo Journalof Agricultura of the University of Puerto Rico vol 63 pp 366ndash376 1979
[89] B Weniger Y Jiang A Oulad-Ali L Italiano J P Beck and RAnton ldquoBiological effects of bixin and Bixa orellana extracts onlymphoid cells in culturerdquo Planta Medica vol 59 no 7 articleA680 1993
[90] CM Chariandy C E Seaforth R H Phelps G V Pollard andB P S Khambay ldquoScreening of medicinal plants from Trinidad
and Tobago for antimicrobial and insecticidal propertiesrdquoJournal of Ethnopharmacology vol 64 no 3 pp 265ndash270 1999
[91] F J R Paumgartten R R Carvalho I B Araujo et alldquoEvaluation of the developmental toxicity of annatto in the ratrdquoFood and Chemical Toxicology vol 40 no 11 pp 1595ndash16012002
[92] C F Spencer F R Koniuszy E F Rogers et al ldquoSurvey of plantsfor antimalarial activityrdquo Lloydia vol 10 no 3 pp 145ndash174 1947
[93] H Mikkelsen J C Larsen and F Tarding ldquoHypersensitivityreactions to food colours with special reference to the naturalcolour annatto extract (butter colour)rdquo Toxicological Aspects ofFood Safety vol 1 pp 141ndash143 1978
Submit your manuscripts athttpwwwhindawicom
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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom
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ToxinsJournal of
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Autoimmune Diseases
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Pharmaceutics
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MEDIATORSINFLAMMATION
of
The Scientific World Journal 3
Table 1 Traditional uses of annatto in American countries
Countryuse Plant part ReferencesArgentina
Antipyreticcardiotonicantidiarrheal Seeds [24]Antidiarrhealdyescondiment Seeds [25]
BrazilBody paint Seeds [26]Insect repellent Seeds [27]Condimentfood coloring Seeds [27]Antipyretic Seeds [26]Antipyreticlaxativesburns Seeds [28]Malaria Seeds [26]
ColombiaSnakebite Leaves [29]Aphrodisiac Seeds [30]
CubaAphrodisiac Seeds [31]
GuatemalaGonorrheadysentery Leaves [32]Hepatitis Leaves [33]Dysentery Leaves [34]Blood diseases Leaves [35]Gonorrhea Roots [32]Diabetes Roots [36]
HondurasAromaticfood coloring Seeds [37]Paindigestivedysentery Leaves [38]
JamaicaDiabetes Seeds [39]
NicaraguaRespiratory and pulmonary disordersdiarrheadiureticburns Leaves + seeds [40]Labor pains Seeds [41]Coughcolddiureticdiarrheaburnslabor pains Seeds [40]
ParaguayInsecticiderepellent Seeds [42]Diabetes Seeds [39]
PeruAphrodisiacaphrodisiacdiureticantidisenteriaastringent Fruits [34]Antipyreticskin problems Leaves [33]Alcoholic hepatitisworms Roots [33]Antipyreticaphrodisiacdysenteryastringentstomach Seeds [34]
Trinidad and TobagoDiuretic Leaves [43]Diabetes Roots [44]Diabetes Roots [45]
Bixin was isolated for the first time from the seeds of Bixaorellana in 1875 and in 1961 its complete chemical structureand stereochemistry were determined by 1H and 13C-NMRBixin belongs to the small class of natural apocarotenoidswhose formation occurs by the oxidative degradation of C40carotenoids (Table 2)
Bixin consists of a chain of 25 carbons and has the molec-ular formula C
25H30O4(MW = 39451) It has a carboxylic
acid and methyl ester group at the ends of the chain Bixinoccurs in nature as 16-119885 (119888119894119904) but during the extractionprocess it isomerizes resulting in the 16-119864 form (trans) whichis called isobixin (Figure 1)
4 The Scientific World Journal
Table 2 The main carotenoids from the seeds of Bixa orellana
Carotenoid Country of isolation Physical aspect ReferencesApo-120595-carotene 91015840Z-61015840-ol Brazil Oil [46]
Beta carotene Brazil 183∘C [47]Suriname lowast [48]
Bixin
Brazil 198∘C [49ndash51]Peru lowast [52]
Dominican Rep lowast [53]Suriname lowast [48]USA lowast [54]
Z-Carotene Brazil Oil [46]Cryptoxanthin Suriname 173∘C [48]Dimethyl-(9Z)-661015840-diapocarotene-661015840-dioate Brazil Oil [52]Dimethyl-(9Z91015840Z)-661015840-diapocarotene-661015840-dioate Brazil Oil [50]Phytoene Brazil Oil [46]Phytofluene Brazil Oil [46]Geranylgeraniol Brazil Oil [52]Lutein Suriname 196∘C [48]Methyl-(9Z)-101015840-oxo-6101015840-diapocarotene-6-oate Brazil Oil [50]Methyl-(9Z)-61015840-oxo-651015840-diapocarotene-6-oate Brazil Oil [50]Methyl-(9Z)-81015840-oxo-681015840-diapocarotene-6-oate Brazil Oil [50]Methyl-(91015840Z)-apo-61015840-lycopenoate Brazil Oil [46]Methyl-(7Z9Z91015840Z)-apo-61015840-lycopenoate Brazil Oil [55]Methyl-(9Z)-apo-81015840-lycopenoate Brazil Oil [46]Methyl-(all-E)-apo-81015840-lycopenoate Brazil Oil [46]Neurosporene Brazil Oil [46]Norbixin Brazil 300∘C [52]Trans-bixin Jamaica 195∘C [56]Zeaxanthin Suriname 215∘C [48]Source [57]
Many other carotenoids (C19 C22 C24 C25 C30 and C
32)
occur in Bixa orellana but constitute a minor percentage ofthe pigments The major oily constituent of annatto seedsis geranylgeraniol representing 1 of dry seeds Norbixin(Figure 1) is a demethylated derivative of bixin and althoughit is a naturally occurring compound it is almost alwaysreferred to as a saponification product of bixin This is theform used for commercial purposes [62]
Currently more than two dozen substances have beenisolated from the seeds of Bixa orellana Besides bixin andnorbixin other compounds such as isobixin beta-carotenecryptoxanthin lutein zeaxanthin orellin bixein bixol cro-cetin ishwarane ellagic acid salicylic acid threonine tomen-tosic acid tryptophan and phenylalanine have been found inthe seeds of annatto In addition the following compounds intheir respective concentrations are found in these seeds 40to 45 cellulose 35 to 55 sugars 03 to 09 essential oils3 fixed oils 10 to 45 pigments and 13 to 16 proteinsand alpha and beta-carotene as well as tannins and saponins[63 64]
Mercadante et al [50 65] isolated eight apocarotenoidsfromannatto seedsmethyl (7Z 9Z 91015840Z)-apo-61015840-lycopenoatemethyl (9Z)-apo-81015840-lycopenoate methyl 1(all-E)-apo-81015840-lycopenoate methyl (all-E)-8-apo-beta-carotene-81015840-oate
methyl (all-E)-apo-61015840-lycopenoate 6-geranylgeranyl-81015840-methyl-681015840diapocaroten-6-81015840dioate 61015840-geranylgeranyl-61015840-methyl-(9Z)-661015840-diapocaroten-6-61015840-dioate and 6-geranylgeranyl-61015840-methyl-6-61015840-diapocaroten-6-61015840-dioate
More than 100 volatile compounds have been detectedin aqueous and organic extracts where 50 of these havealready been identified (eg bornyl acetateprop-caryophyllenecopaene prop-cubebene (+)-cyclosativene geranyl phenylac-etate 1-heptanetiol 3-methylpyridine 4-methylpyridine 120574-elemene 120573-humulene isoledene 120573-pinene seline-6-en-4-ol120575-selinene (minus)-spathulenol and (+)-ylangene) [66]
Because annatto is a rich source of carotenoids it isof great commercial importance In fact the therapeuticproperties of annatto (eg antioxidant and hypoglycemic)have been attributed to its high levels of carotenoids [67ndash69]Table 2 lists some of these compounds
The pigments in annatto seeds can be extracted bymechanical processes through grinding the seeds and byphysical-chemical methods using solvents or enzymes [46]The solvent extraction can be performed using three basicmethods alkaline extraction (NaOH or KOH solutions)which results in the conversion of bixin to norbixinextraction with oil (soybean corn) and extraction usingorganic solvents (hexane chloroform ethanol acetone or
The Scientific World Journal 5
Bixin (Z-bixin or cis-bixin)
COOH
COOMe
116
(a)
MeOOC 16 1
Isobixin (E-bixin or trans-bixin)
COOH
(b)
COOHHOOC
Norbixin
(c)
OH
Geranylgeraniol
(d)
Figure 1 Chemical structure of some pigments of annatto
propylene glycol) which results in the purest form of pig-ments
Barbosa-Filho et al [49] studied the seeds of four typesof annatto cultivated in Paraıba State Brazil namely ldquocas-caverderdquo (ldquogreen peelrdquo) ldquocascavermelhardquo (ldquored barkrdquo) ldquobicode calangordquo (ldquolizard beakrdquo) and ldquograopretordquo(ldquoblack grainrdquo)with respect to their oil (material extracted with hexane)and solid (material extracted with chloroform) contentsand also pure bixin which was obtained by successiverecrystallization from the chloroform fraction Pure bixinappears as red-purple crystals with a melting point of 196ndash198∘CThe different concentrations found for the oil fractionchloroform extract and bixin are as follows red bark 58lizard beak 51 green peel 49 and black grain 46 Redbark shows the highest yield for both solvent fractions andthe bixin amount is around 1This species has been reportedas the most used in folk medicine On the other hand blackgrain shows negligible amounts of bixin
6 Biological Activity
Table 3 shows data found in 38 studies performed withannatto in 15 different countries in the American countriesTo obtain the extracts and fractions tested several plant partswere used such as leaf root seed shoot and even the wholeplant The data surveyed were classified according to thepharmacological activity tested
Among the twenty-one activities tested those with thelargest number of studies performed were antifungal activity(12) antibacterial activity (12) antimalarial activity (6) andmutagenic activity (3) Cytotoxic activity and toxicity havebeen little studied with three and two studies respectivelyPharmacological activities have been evaluated in animalmodels (22 preclinical studies) human models (1 clinicalstudy) cell cultures (2 studies) and in vitro tests (32 studies)
Antifungal activity has been investigated in one countryin Central America (Guatemala) and in two countries inSouth America (Ecuador and Argentina) using eleven differ-ent fungal strains [70 82 84]
Freixa et al [82] conducted a study in Ecuador to assessthe antifungal activity of extracts from the dried leaves of
the annatto tree in response to 7 fungi species obtainingsatisfactory antifungal activity against Trichophyton menta-grophytes trains In Guatemala three different strains wereused to evaluate antifungal activity with no satisfactoryactivity being observed [84]
The extracts of annatto leaves have been evaluated forantibacterial activity against 8 different bacterial strains(Bacillus subtilis Escherichia coli Micrococcus luteus Pseu-domonas aeruginosa Staphylococcus aureus Salmonella typhiShigella dysenteriae and Staphylococcus epidermidis) show-ing no activity
Antimalarial activity has been determined against Plas-modium gallinaceum Plasmodium lophurae andPlasmodiumberghei Although the studies conducted previously in theUnited States did not show significant results [92] Valdes etal (2011) reported a moderate activity of the seed extracts ofBixa orellana against Plasmodium berghei and falciparum
7 Mutagenic and Cytotoxic Activities
No significant effect was observed when extracts of annattoseeds were tested for mutagenic activity in studies performedin the United States and Brazil [67 93]
Extracts obtained from annatto seeds and leaves havebeen tested in cell cultures and the brine shrimp assayrespectively and have been found to lack cytotoxicity ineither model used These experiments were carried out inGuatemala and the Dominican Republic [83 89]
On the other hand a study performed in Cuba with 10medicinal plants that were active in inhibiting human lungcarcinoma cell growth showed that the ethanolic extract ofBixa orellana presented cytotoxicity at concentrations below100 120583gmL [81]
8 Toxicological Activities
Currently concerns about the effect of synthetic dyes onhuman health are incontestable making people increasinglychoose those of natural origin believing that they are devoidof toxic effects This is not entirely true because even amedication from a natural source can be a poison depending
6 The Scientific World Journal
Table3Biologicalactiv
ities
ofextractsof
annatto
inAmerican
coun
tries
Cou
ntry
biologicalactiv
ityPartused
Type
ofextract
Organism
teste
dMod
elteste
dDoseu
sed
Activ
ityRe
ferences
Argentin
aAntibacteria
lLE
EtOH
Bacillussubtilis
Invitro
5mgmL
Inactiv
e[70]
Escherich
iacoli
Invitro
5mgmL
Inactiv
e[70]
Micrococcusluteus
Invitro
5mgmL
Inactiv
e[70]
Pseudomonas
aeruginosa
Invitro
5mgmL
Inactiv
e[70]
Staphylococcus
aureus
Invitro
5mgmL
Inactiv
e[70]
Antifu
ngal
LEEtOH
Aspergillus
niger
Invitro
5mgmL
Inactiv
e[70]
Cand
idaalbicans
Invitro
5mgmL
Inactiv
e[70]
Antivira
lSE
EtOH
VirusH
erpessim
plex
1Cell
cultu
re078
mgmL
Inactiv
e[71]
Insecticidal
AP
MeO
HInsect
Sitophilu
soryzae
5Inactiv
e[71]
Brazil
Antim
alarial
SECH
Cl3
Mou
sePlasmodium
berghei
100m
gkg
Inactiv
e[26]
Antioxidant
SEEtOH
Invitro
DPP
Hassay
01g
Lminus1
Activ
e[6]
Insectrepellent
SEPetr
eth
Ham
ster
Lutzom
yialongipalpis
1gL
Activ
e[72]
SEEtOH
Mosqu
itoAe
desa
egypti
182mgmL
Activ
e[6]
Molluscicidal
SEEtOH
Con
chBiom
phalariagla
brata
10000
ppm
Inactiv
e[73]
Mutagenic
Powder
Mou
seBo
nemarrowcells
10670
ppm
Inactiv
e[67]
Toxicity
SEPo
wder
Rat
Invivo
500m
gkg
Inactiv
e[74]
Antileish
manial
LERO
EtOH
Leish
maniaam
azonensis
Invitro
012ndash25mgmL
Activ
e[75]
Antileish
manial
SEOE
Leish
maniaam
azonensis
Invitro
10501005001000120583gmL
Activ
e[76]
Hyperlip
idem
iaSE
H2O
Mou
seIn
vitro
400and800m
gkg
Activ
e[77]
Colom
bia
Snakebite
LEEtOH
Mou
seBo
throps
atrox
LD50gt260120583
ganim
alAc
tive
[29]
CostaRica
Anti-infl
ammatory
ROEtOH
Rat
Pawedem
acarrageenan
100m
gkg
Inactiv
e[78]
Cuba Positiveino
tropice
ffect
AP
H2O
Guineap
igIsolated
atriu
m320120583
LInactiv
e[79]
Antim
alarial
SEPlasmodium
gallina
ceum
falciparum
Invivoin
vitro
500m
gkg
Activ
e[80]
Cytotoxic
SEEtOH
Tumor
cells
Invitro
39ndash
250m
gmL
Activ
e[81]
Ecuado
rAntifu
ngal
LEMeO
HAspergillus
niger
Invitro
10mgdisk
Inactiv
e[82]
Cand
idaalbicans
Invitro
10mgdisk
Inactiv
e[82]
Cryptococcus
neoforman
sIn
vitro
10mgdisk
Inactiv
e[82]
Fusariu
moxysporum
Invitro
10mgdisk
Inactiv
e[82]
Neurospora
crassa
Invitro
10mgdisk
Inactiv
e[82]
Penicilliu
mpurpurogenum
Invitro
10mgdisk
Inactiv
e[82]
Trich
ophytonmentagrophytes
Invitro
10mgdisk
Activ
e[82]
The Scientific World Journal 7
Table3Con
tinued
Cou
ntry
biologicalactiv
ityPartused
Type
ofextract
Organism
teste
dMod
elteste
dDoseu
sed
Activ
ityRe
ferences
Guatemala
Antibacteria
lLE
Vario
usEscherich
iacoli
Invitro
50120583Ldisk
Inactiv
e[83]
Pseudomonas
aeruginosa
Invitro
MICgt10mgmL
Inactiv
e[83]
Salm
onellatyphi
Invitro
MICgt10mgmL
Inactiv
e[83]
Shigelladysenteriae
Invitro
50120583L
Inactiv
e[83]
Staphylococcus
aureus
Invitro
MICgt10mgmL
Inactiv
e[83]
Antifu
ngal
LEH
2OAspergillus
flavus
Invitro
MICgt10mgmL
Inactiv
e[84]
Cand
idaalbicans
Invitro
MICgt10mgmL
Inactiv
e[84]
Microsporum
gypseum
Invitro
MICgt10mgmL
Inactiv
e[84]
Antigon
orrheal
LEEtOH
Neisseriagonorrhea
Invitro
50120583Ldisk
Activ
e[32]
Antitrypanosom
alLE
EtOH
Trypanosom
acruzi
Invitro
MICgt1m
gmL
Inactiv
e[83]
Cytotoxic
LEH
2OCr
ustacean
Artemiasalin
aLC
50gt10
00pp
mInactiv
e[83]
Inhibof
plateletaggregation
SE
Invitro
Thrombinaggregation
IC50
0795m
gmL
Inactiv
e[35]
Haw
aii
Con
traceptiv
eRO
Mou
se
02m
Lanim
alInactiv
e[85]
Jamaica
Hypoglycemic
SECH
Cl3
Dog
1gAc
tive
[39]
H2O
Dog
200m
Lanim
alAc
tive
[39]
Antioxidant
SEEtOH
Invitro
Invitro
025
and25120583
gmL
Activ
e[86]
Mexico
Allergenic
SEOil
Hum
an25120583L
person
Activ
e[87]
Paragu
ayInsecticidal
SEPetr
ether
Insect
Rhodnius
negle
ctus
50120583g
Inactiv
e[42]
Puerto
Rico
Molluscicidal
TPH
2OCon
chLymna
eacubensis
LD100gt1M
ppm
Inactiv
e[88]
Dom
inican
Repu
blic
Cytotoxic
SEEtOH
Cellculture
Molt4
cells
200120583
gmL
Inactiv
e[89]
Trinidad
andTo
bago
Antibacteria
lSE
EtOAc
Escherich
iacoli
Invitro
1000120583gmL
Inactiv
e[90]
Pseudomonas
aeruginosa
Invitro
1000120583gmL
Inactiv
e[90]
USA A
nticon
vulsa
ntRA
EtOH
Mou
seSeizureselectroshock
100m
gkg
Inactiv
e[91]
Rat
Seizurespentylenetetrazole
400m
gkg
Inactiv
e[91]
Antim
alarial
SECH
Cl3
Chicken
Plasmodium
gallina
ceum
388m
gkg
Inactiv
e[92]
Mutagenic
SEMeO
HSalm
onellatyphim
urium
100m
gplaque
Inactiv
e[93]
H2O
Invitro
Placentaltroph
oblasts
100m
gplaque
Inactiv
e[93]
Hypotensiv
eRA
EtOH
Rat
50mgkg
Activ
e[93]
Toxicity
RAH
2OMou
seLD
50gt700m
gkg
Inactiv
e[92]
LEleafAP
aeria
lpartTP
totalplantRO
roo
tSE
seedno
tgivenLD5050
lethaldo
seIC5
0concentrationthatinhibits50of
thee
ffectM
ICm
inim
uminhibitory
concentration
8 The Scientific World Journal
on the dose that is administered The failure to require in-depth data related to toxicological and chemical analysesfor the registration of food additives derived from naturalsources [67 74] certainly makes the information aboutpossible unwanted effects andor pharmacological activitiesresulting from their use much rarer than expected in view ofthe importance of the topic In Brazil the use of annatto is sowidespread that its safety is not even questioned
Paumgartten et al [91] evaluated the toxicity of annattoextracts in rats Doses up to 500mgkg body weightdaywere introduced directly into the stomach of pregnant ratsto evaluate the effect on the mother and fetus and noadverse effects were found for either The annatto extract didnot induce an increase in the incidence of visible externalvisceral or skeletal anomalies in the fetuses Therefore thestudy suggested that the annatto extract was not toxic to ratsnor was it embryotoxic Studies performed in Brazil by Alvesde Lima et al [67] where extracts of annatto weremixed withthe food of male rats showed that the concentrations testedhad no mutagenic or antimutagenic activity in their bonemarrow cells A parallel toxicity study conducted byHagiwaraet al [74] showed that 01 annatto extract administered forthirteen weeks in the feed of male and female rats did notshow any adverse effects However when higher doses wereadministered (03 and 09) the authors noticed an increasein liver weight as well as changes in blood chemistriesincluding increase in alkaline phosphatase phospholipidsand total protein as well as albumin and albuminglobulinratio
Hagiwara et al [74] also evaluated extracts of annattofor liver carcinogenicity in rats and found no evidence ofliver tumors even when given to animals at a high dose of200mgkg body weightday compared to an acceptable doseof 00 to 0065mgkgday thus indicating that the dangerof a hepatocarcinogenic effect in humans may be absent ornegligible
A toxicity test was performedwith extracts obtained fromboth plant seeds and shoots and no significant effect wasobserved The experiments were performed in the UnitedStates using mice as the animal model and it was found thatthe LD50 was greater than 700mgkg [92]
9 Correlation between the BiologicalActivities Phytochemistry and theTraditional Uses of Bixa orellana
Table 1 shows that many of the traditional uses of Bixaorellana are the same in several countries of South andCentral America which suggests its effectiveness as a ther-apeutic agent Extracts of Bixa orellana showed biologicalactivities such as antioxidant hypotensive molluscicideand antimalarial against A549 cells for carcinoma of thelung allergy hypoglycemic antifungal antioxidant insectrepellent antigonococcal and antivenom serum and some ofthem are in accordance with the traditional use for examplein Brazil it is used to extract the seeds with purpose repellentinsecticide and antimalaria and scientific studies in the samecountrywith the Lutzomyia longipalpis insect repellent action
and prove a study in Cuba proved the pharmacological actionfor antimalarial activity when tested against Plasmodiumberghei Some of them are in accordance with the traditionaluse for example seed extracts have been used in Brazil andCuba as insect repellent and antimalarial Antioxidant andinsect repellent activities can be attributed to the carotenoidsand the essential and fixed oils respectively
Despite the previous reports about the presence of com-ponents with anti-inflammatory properties such as salicylicacid lutein polyphenols and tannins this activity has not yetbeen proven for Bixa orellana extracts Similarly the plantrsquosessential and fixed oils have shown antibacterial propertiesalthough this activity has not been proven too
In general the data obtained in this review do not allowcorrelations between the biologic activities tested in vitro or invivo with the compounds identified in this species Howevertaking into account the related activities such as the antipara-sitic effect and the lack of mutagenic and cytotoxicity activityit is possible to consider Bixa orellana as a potential source forthe development of phytopharmaceutical products
In conclusion the studies discussed in this review repre-sent a rich database around the Bixa orellana activities andits potential uses which evokes the feasibility of phytophar-maceuticals to treat some diseases whenever an antioxidanthypotensor or hypoglycemiant activity is necessary
Although the commercial exploitation of this species iswell established there are very few studies on its pharma-cological effects Considering the need for developing a safeand effective product more studies should be performed inorder to confirm other biological activities supported by thepopular uses of Bixa orellana
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors are grateful to CNPqPRONEXFAPESQ andCAPES for financial support and to the NAPRALERTDatabase of the University of Illinois USA for the literatureon Bixa orellana A Leyva helped in editing the Englishlanguage of the paper
References
[1] M B Perecin O A Bovi and N B Maia ldquoPesquisa complantas aromaticas medicinais corantes o papel do InstitutoAgronomicordquo O Agronomico vol 54 pp 21ndash24 2002
[2] M E A Elias G Schroth J L V Macedo M S S Motaand S A DrsquoAngelo ldquoMineral nutrition growth and yields ofannatto trees (Bixa orellana) in agroforestry on an AmazonianFerralsolrdquo Experimental Agriculture vol 38 no 3 pp 277ndash2892002
[3] A R R Bastos J G Carvalho R P Assis and A B C FilholdquoMarcha de absorcao de nutrientes em urucum ( Bixa orellanaL) tipo cultivado piave vermelha em fase de viveirordquoCerne vol5 pp 76ndash85 1999
The Scientific World Journal 9
[4] E PThomasM Colvin S B Rosen C Zuccarini and S PetzerldquoHIV prevalence study and costing analysis undertaken for thedevelopment of an HIVAIDS workplace strategy for buffalocity municipalityrdquo Tech Rep Medical Research Council Buf-falo NY USA 2005
[5] C F Franco ldquoO Agronegocio do urucum na regiao Nordesterdquo 1Reuniao Nacional da Cadeia Produtiva de Urucum CD-Rom2007
[6] A Giorgi P De Marinis G Granelli L M Chiesa and SPanseri ldquoSecondary metabolite profile antioxidant capacityand mosquito repellent activity of Bixa orellana from BrazilianAmazon regionrdquo Journal of Chemistry vol 2013 Article ID409826 10 pages 2013
[7] J S Silva M D Moura R A G Oliveira M F F Dinizand J M Barbosa-Filho ldquoNatural product inhibitors of ovarianneoplasiardquo Phytomedicine vol 10 no 2-3 pp 221ndash232 2003
[8] F C F Sousa C T V Melo C O M Cito et al ldquoPlantasmedicinais e seus constituintes bioativos uma revisao dabioatividade e potenciais benefıcios nos disturbios da ansiedadeem modelos animaisrdquo Revista Brasileira de Farmacognosia vol18 pp 642ndash654 2008
[9] L J Quintans Jr J R G S Almeida J T Lima et al ldquoPlantswith anticonvulsant propertiesmdasha reviewrdquo Revista Brasileira deFarmacognosia vol 18 pp 798ndash819 2008
[10] HD S Falcao J A Leite JM Barbosa-Filho et al ldquoGastric andduodenal antiulcer activity of alkaloids a reviewrdquoMolecules vol13 no 12 pp 3198ndash3223 2008
[11] H S Falcao I R Mariath M F F M Diniz L M Batista andJ M Barbosa-Filho ldquoPlants of the American continent withantiulcer activityrdquo Phytomedicine vol 15 no 1-2 pp 132ndash1462008
[12] I R Mariath H D S Falcao J M Barbosa-Filho et al ldquoPlantsof the American continent with antimalarial activityrdquo RevistaBrasileira de Farmacognosia vol 19 no 1 pp 158ndash192 2009
[13] J E R Hon P M Soares C L Melo et al ldquoAtividadefarmacologica da monocrotalina isolada de plantas do generoCrotalariardquo Revista Brasileira de Farmacognosia vol 20 pp453ndash458 2010
[14] R N Almeida D S Navarro and J M Barbosa-Filho ldquoPlantswith central analgesic activityrdquo Phytomedicine vol 8 no 4 pp310ndash322 2001
[15] N Z T Jesus H S Falcao I F Gomes et al ldquoTanninspeptic ulcers and related mechanismsrdquo International Journal ofMolecular Sciences vol 13 no 3 pp 3203ndash3228 2012
[16] L G Rocha J R G S Almeida R O Macedo and J MBarbosa-Filho ldquoA review of natural products with antileishma-nial activityrdquo Phytomedicine vol 12 no 6-7 pp 514ndash535 2005
[17] G R M Lima C A Montenegro C L F Almeida PF Athayde-Filho J M Barbosa-Filho and L M BatistaldquoDatabase survey of anti-inflammatory plants in South Amer-ica a reviewrdquo International Journal ofMolecular Sciences vol 12no 4 pp 2692ndash2749 2011
[18] K S De Lira Mota G E N Dias M E F Pinto et alldquoFlavonoids with gastroprotective activityrdquo Molecules vol 14no 3 pp 979ndash1012 2009
[19] A L Souto J F Tavares M S da Silva M F F M de Diniz P Fde Athayde-Filho and J M Barbosa Filho ldquoAnti-inflammatoryactivity of alkaloids an update from 2000 to 2010rdquo Moleculesvol 16 no 10 pp 8515ndash8534 2011
[20] F L Silva D C H Fischer J F Tavares M S Silva P Fde Athayde-Filho and J M Barbosa-Filho ldquoCompilation of
secondary metabolites from Bidens pilosa LrdquoMolecules vol 16no 2 pp 1070ndash1102 2011
[21] J R Filho H de Sousa Falcao L M Batista J M B Filho andM R Piuvezam ldquoEffects of plant extracts on HIV-1 proteaserdquoCurrent HIV Research vol 8 no 7 pp 531ndash544 2010
[22] JM Barbosa-Filho A A Alencar X P Nunes et al ldquoSources ofalpha- beta- gamma- delta- and epsilon-carotenes a twentiethcentury reviewrdquo Revista Brasileirta de Farmacogn vol 18 no 1pp 135ndash154 2008
[23] S N S Silva C L F Amaral and T N H Reboucas ldquoAdoptionof conservation practices on farm and selection of varieties byproducers of annatto in the city of Vitoria da Conquista-BArdquoRevista Brasileira de Agroecologica vol 5 pp 106ndash113 2010
[24] A L Bandoni M E Mendiondo R V D Rondina and J DCoussio ldquoSurvey of Argentine medicinal plants I Folklore andphytochemical screeningrdquo Lloydia vol 35 no 1ndash4 pp 69ndash801972
[25] G H Garcia R Campos R A de Torres et al ldquoAntiherpeticactivity of some Argentine medicinal plantsrdquo Fitoterapia vol61 no 6 pp 542ndash546 1990
[26] M G L Brandao T S M Grandi E M M Rocha D RSawyer and A U Krettli ldquoSurvey of medicinal plants used asantimalarials in the Amazonrdquo Journal of Ethnopharmacologyvol 36 no 2 pp 175ndash182 1992
[27] M P Correa Dicionario das Plantas Uteis do Brasil e dasExoticas Cultivadas vol 4 Ministerio da AgriculturaIBDF Riode Janeiro Brasil 1978
[28] G S Hirschmann and A R de Arias ldquoA survey of medicinalplants of minas gerais Brazilrdquo Journal of Ethnopharmacologyvol 29 no 2 pp 159ndash172 1990
[29] R Otero R Fonnegra S L Jimenez et al ldquoSnakebites andethnobotany in the northwest region of Colombia Part Itraditional use of plantsrdquo Journal of Ethnopharmacology vol 71no 3 pp 493ndash504 2000
[30] H Garcia-Barriga Flora Medicinal de Colombia vol 2 Univer-sidad Nacional Bogota Colombia 1975
[31] J T Roig y Mesa Plantas Medicinales Aromaticas o Venenosasde Cuba Ministerio de Agricultura Havana Cuba 1945
[32] A Caceres H Menendez E Mendez et al ldquoAntigonorrhoealactivity of plants used inGuatemala for the treatment of sexuallytransmitted diseasesrdquo Journal of Ethnopharmacology vol 48no 2 pp 85ndash88 1995
[33] J A Duke and R V Martinez Amazonian EthnobotanicalDictionary CRC Press Boca Raton Fla USA 1994
[34] V R Ramirez L J Mostacero A E Garcia et al VegetalesEmpleados enMedicina Tradicional Norperuana Banco Agrariodel Peru Universidad Nacional de Trujillo Trujillo Peru 1988
[35] R Villar J M Calleja C Morales and A Caceres ldquoScreeningof 17 Guatemalan medicinal plants for platelet antiaggregantactivityrdquo Phytotherapy Research vol 11 pp 441ndash445 1997
[36] L M Giron V Freire A Alonzo and A Caceres ldquoEthnob-otanical survey of the medicinal flora used by the Caribs ofGuatemalardquo Journal of Ethnopharmacology vol 34 no 2-3 pp173ndash187 1991
[37] D L Lentz ldquoMedicinal and other economic plants of the PayaofHondurasrdquo Economic Botany vol 47 no 4 pp 358ndash370 1993
[38] D L Lentz A M Clark C D Hufford et al ldquoAntimi-crobial properties of Honduran medicinal plantsrdquo Journal ofEthnopharmacology vol 63 no 3 pp 253ndash263 1998
[39] E Y Morrison and M E West ldquoThe effect of Bixa orellana(Annatto) on blood sugar levels in the anaesthetized dogrdquoWestIndian Medical Journal vol 34 no 1 pp 38ndash42 1985
10 The Scientific World Journal
[40] F G Coe and G J Anderson ldquoScreening of medicinal plantsused by the Garıfuna of eastern Nicaragua for bioactive com-poundsrdquo Journal of Ethnopharmacology vol 53 no 1 pp 29ndash501996
[41] B Barrett ldquoMedicinal plants of Nicaraguarsquos Atlantic CoastrdquoEconomic Botany vol 48 no 1 pp 8ndash20 1994
[42] G Schmeda-Hirschmann and A R de Arias ldquoA screeningmethod for natural products on triatomine bugsrdquo PhytotherapyResearch vol 6 no 2 pp 68ndash73 1992
[43] G E Simpson ldquoFolk medicine in Trinidadrdquo The Journal ofAmerican Folklore vol 75 no 298 pp 326ndash340 1962
[44] D Mahabir and M C Gulliford ldquoUse of medicinal plants fordiabetes in Trinidad and Tobagordquo Revista Panamericana deSalud Publica vol 1 no 3 pp 174ndash179 1997
[45] E S Ayensu ldquoMedicinal plants of theWest IndiesrdquoUnpublishedManuscript 1978
[46] A Z Mercadante A Steck D Rodriguez-Amaya H Pfanderand G Britton ldquoIsolation of methyl 91015840Z-APO-61015840-lycopenoatefrom Bixa Orellanardquo Phytochemistry vol 41 no 4 pp 1201ndash1203 1996
[47] E Angelucci H K Arima E A Kumagai and I AnnattoldquoPreliminary data of the chemical compositionrdquo Coletanea doInstituto de Tecnologia de Alimentos vol 11 pp 89ndash96 1980
[48] A S L Tirimanna ldquoStudy of the carotenoid pigments of Bixaorellana L Seeds by thin layer chromatographyrdquo MikrochimicaActa vol 76 no 1-2 pp 11ndash16 1981
[49] J M Barbosa-Filho R N Silva-Filho B F Lira et al ldquoTeor debixina em quatro variedades de Bixa orellana L cultivadas naParaıbardquo Revista Brasileira de Farmacognosia vol 7-8 pp 41ndash47 1998
[50] A Z Mercadante A Steck and H Pfander ldquoIsolation andstructure elucidation of minor carotenoids from annatto (Bixaorellana L) seedsrdquo Phytochemistry vol 46 no 8 pp 1379ndash13831997
[51] C Prentice-Hernandez and O Rusig ldquoAnnatto (Bixa orellanaL) extract obtained using ethyl alcohol as a solventrdquo Arquivosde Biologia e Tecnologia vol 35 pp 63ndash74 1992
[52] A Z Mercadante ldquoComposition of carotenoids from annattordquoACS Symposium Series vol 775 pp 92ndash101 2001
[53] M J Scotter L A Wilson G P Appleton and L CastleldquoAnalysis of Annatto (Bixa orellana) Food Coloring Formula-tions 1 Determination of Coloring Components and ColoredThermal Degradation Products by High-Performance LiquidChromatography with Photodiode Array Detectionrdquo Journal ofAgricultural and Food Chemistry vol 46 no 3 pp 1031ndash10381998
[54] A J Degnan J H von Elbe and R W Hartel ldquoExtraction ofannatto seed pigment by supercritical carbon dioxiderdquo Journalof Food Science vol 56 pp 1655ndash1659 1991
[55] A ZMercadante A Steck andH Pfander ldquoIsolation and iden-tification of new apocarotenoids from annatto (Bixa orellana)seedsrdquo Journal of Agricultural and Food Chemistry vol 45 no4 pp 1050ndash1054 1997
[56] S G Anderson M G Nair A Chandra and E MorrisonldquoSupercritical fluid carbon dioxide extraction of annatto seedsand quantification of trans-bixin by high pressure liquid chro-matographyrdquo Phytochemical Analysis vol 8 pp 247ndash249 1997
[57] J M Barbosa-Filho Bixa orellana Retrospectiva de usos pop-ulares atividades biologicas fitoquımica e emprego na fito-cosmetica no continente americano Simposio Brasileiro doUrucummdashSIMBRAU Joao Pessoa Brazil 2006
[58] J Revilla Plantas da Amazonia Oportunidades Economicas eSustentaveis Manaus Programa de Desenvolvimento Empre-sarial e Tecnologico 2nd edition 2001
[59] F Oliveira G Akisue and M K Akisue FarmacognosiaAtheneu Sao Paulo Brazil 1996
[60] J Alonso Tratado de Fitofarmacos y Nutraceuticos CorpusRosario Argentina 2004
[61] C O Franco E G Fabri M Barreiro Neto M H Manfiolli MN C Harder and N C Rucker Urucum Sistema de Producaopara o Brasil Emepa-Pb Apta Joao Pessoa Brazil 2008
[62] P A Venugopalan G A Giridhar and A G RavishankarldquoFood Ethanobotanical and diversified applications of Bixaorellana L a scope for its improvement through biotechnolog-ical mediationrdquo Indian Journal of Fundamental and Applied LifeSciences vol 1 pp 9ndash31 2011
[63] L Taylor Herbal Secrets of the Rainforest Sage Press RocklinCalif USA 2nd edition 2002
[64] J S Oliveira Caracterizacao Extracao e Purificacao por Cro-matografia de Compostos de Urucum (Bixa orellana L) [tesisdoctoral en Ingenierıa Quımic] Universidade Federal de SantaCatarina Florianopolis Brazil 2005
[65] A Z Mercadante A Steck and H Pfander ldquoThree minorcarotenoids from annatto (Bixa orellana) seedsrdquo Phytochem-istry vol 52 no 1 pp 135ndash139 1999
[66] V Galindo-Cuspinera M B Lubran and S A Rankin ldquoCom-parison of volatile compounds in water- and oil-soluble annatto(Bixa orellana L) extractsrdquo Journal of Agricultural and FoodChemistry vol 50 no 7 pp 2010ndash2015 2002
[67] R O Alves de Lima L Azevedo L R Ribeiro and D M FSalvadori ldquoStudy on the mutagenicity and antimutagenicity ofa natural food colour (annatto) in mouse bone marrow cellsrdquoFood and Chemical Toxicology vol 41 no 2 pp 189ndash192 2003
[68] L R P Lima T T Oliveira T J Nagem et al ldquoBixina norbixinae quercetina e seus efeitos no metabolismo lipıdico de coelhosrdquoBrazilian Journal of Veterinary Research andAnimal Science vol38 pp 196ndash200 2001
[69] J D Fontana S V Mendes D S Persike L F Peracetta andM Passos ldquoCarotenoides cores atraentes e acao biologicardquoBiotecnologia Ciencia amp Desenvolvimento vol 2 p 13 2000
[70] C A Penna M Radice G O Gutkind et al ldquoAntibacterial andantifungal activities of some Argentinean plantsrdquo Fitoterapiavol 65 no 2 pp 172ndash174 1994
[71] A M Broussalis G E Ferraro V S Martino R Pinzon J DCoussio and J C Alvarez ldquoArgentine plants as potential sourceof insecticidal compoundsrdquo Journal of Ethnopharmacology vol67 no 2 pp 219ndash223 1999
[72] A Rojas de Arias G Schmeda-Hirschmann and A FalcaoldquoFeeding deterrency and insecticidal effects of plant extracts onLutzomyia longipalpisrdquo Phytotherapy Research vol 6 no 2 pp64ndash67 1992
[73] M S Pinheiro and M Z Rouquayrol ldquoMolluscicidal activityof plants from Northeast Brazilrdquo Revista Brasileira de PesquisasMedicas e Biologicas vol 7 pp 389ndash394 1974
[74] A Hagiwara N Imai T Ichihara et al ldquoA thirteen-week oraltoxicity study of annatto extract (norbixin) a natural food colorextracted from the seed coat of annatto (Bixa orellana L) inSprague-Dawley ratsrdquoFood andChemical Toxicology vol 41 no8 pp 1157ndash1164 2003
[75] C R Almeida R B Silva M J Marques and J K ChavascoldquoEvaluation of antiparasitic activity of hydroethanolic extractsfrom root stem and leaf of Bixa orellana L on Leishmania
The Scientific World Journal 11
amazonensis samplesrdquo Revista da Universidade Vale do RioVerde vol 10 no 2 pp 384ndash391 2012
[76] M V Lopes V C Desoti A D O Caleare T Ueda-NakamuraS O Silva and C V Nakamura ldquoMitochondria superoxideanion production contributes to geranylgeraniol-induced deathin leishmania amazonensisrdquo Evidence-Based Complementaryand Alternative Medicine vol 2012 Article ID 298320 9 pages2012
[77] J M Ferreira D F Sousa M B Dantas et al ldquoEffects of BixaorellanaL seeds onhyperlipidemiardquoPhytotherapyResearch vol27 no 1 pp 144ndash147 2013
[78] P S BenoitHH S FongGH Svoboda andN R FarnsworthldquoBiological and phytochemical evaluation of plants XIV Anti-inflammatory evaluation of 163 species of plantsrdquo Lloydia vol39 no 2-3 pp 160ndash171 1976
[79] D Carabajal A Casaco L Arruzazabala R Gonzalez andV Fuentes ldquoPharmacological screening of plant decoctionscommonly used in Cuban folk medicinerdquo Journal of Ethnophar-macology vol 33 no 1-2 pp 21ndash24 1991
[80] A F C Valdes J M Martınez D A Rodrıguez R S Lizamaand Y G Gaiten ldquoActividad antimalarica de un extractohidroalcoholico de Bixa orellanaLrdquo Revista Cubana de Medic-ina Tropical vol 63 pp 181ndash185 2011
[81] A D Garcıa H R Sanchez and R S Lizama ldquoCitotoxicidadde extractos de plantas medicinales sobre la lınea celularde carcinoma de pulmon humano A549rdquo Revista Cubana deFarmacia vol 45 pp 101ndash108 2011
[82] B Freixa R Vila L Vargas N Lozano T Adzet and SCanigueral ldquoScreening for antifungal activity of nineteen LatinAmerican plantsrdquo Phytotherapy Research vol 12 no 6 pp 427ndash430 1998
[83] A Caceres B Lopez S Gonzalez I Berger I Tada and JMaki ldquoPlants used in Guatemala for the treatment of pro-tozoal infections I Screening of activity to bacteria fungiand American trypanosomes of 13 native plantsrdquo Journal ofEthnopharmacology vol 62 no 3 pp 195ndash202 1998
[84] A Caceres O Cano B Samayoa and L Aguilar ldquoPlants usedin Guatemala for the treatment of gastrointestinal disorders1 Screening of 84 plants against enterobacteriardquo Journal ofEthnopharmacology vol 30 no 1 pp 55ndash73 1990
[85] A S Matsui S Hoskin M Kashiwagi et al ldquoA survey ofnatural products from Hawaii and other areas of the Pacificfor an antifertility effect in micerdquo Internationale Zeitschrift furKlinische PharmakologieTherapie und Toxikologie vol 5 no 1pp 65ndash69 1971
[86] M Abayomi A S Adebayo D Bennett R Porter and JS Campbell ldquoIn vitro antioxidant activity of Bixa orellana(Annatto) seed extractrdquo Journal of Applied PharmaceuticalScience vol 4 no 2 pp 101ndash106 2014
[87] NW Dunham and K R Allard ldquoA preliminary pharmacologicinvestigation of the roots of Bixa orellanardquo Journal of theAmerican Pharmacist Associantion vol 49 pp 218ndash219 1960
[88] F RMedina andRWoodbury ldquoTerrestrial plantsmolluscicidalto lymnaeid hosts of Fasciliasis hepatica in Puerto Ricordquo Journalof Agricultura of the University of Puerto Rico vol 63 pp 366ndash376 1979
[89] B Weniger Y Jiang A Oulad-Ali L Italiano J P Beck and RAnton ldquoBiological effects of bixin and Bixa orellana extracts onlymphoid cells in culturerdquo Planta Medica vol 59 no 7 articleA680 1993
[90] CM Chariandy C E Seaforth R H Phelps G V Pollard andB P S Khambay ldquoScreening of medicinal plants from Trinidad
and Tobago for antimicrobial and insecticidal propertiesrdquoJournal of Ethnopharmacology vol 64 no 3 pp 265ndash270 1999
[91] F J R Paumgartten R R Carvalho I B Araujo et alldquoEvaluation of the developmental toxicity of annatto in the ratrdquoFood and Chemical Toxicology vol 40 no 11 pp 1595ndash16012002
[92] C F Spencer F R Koniuszy E F Rogers et al ldquoSurvey of plantsfor antimalarial activityrdquo Lloydia vol 10 no 3 pp 145ndash174 1947
[93] H Mikkelsen J C Larsen and F Tarding ldquoHypersensitivityreactions to food colours with special reference to the naturalcolour annatto extract (butter colour)rdquo Toxicological Aspects ofFood Safety vol 1 pp 141ndash143 1978
Submit your manuscripts athttpwwwhindawicom
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MEDIATORSINFLAMMATION
of
4 The Scientific World Journal
Table 2 The main carotenoids from the seeds of Bixa orellana
Carotenoid Country of isolation Physical aspect ReferencesApo-120595-carotene 91015840Z-61015840-ol Brazil Oil [46]
Beta carotene Brazil 183∘C [47]Suriname lowast [48]
Bixin
Brazil 198∘C [49ndash51]Peru lowast [52]
Dominican Rep lowast [53]Suriname lowast [48]USA lowast [54]
Z-Carotene Brazil Oil [46]Cryptoxanthin Suriname 173∘C [48]Dimethyl-(9Z)-661015840-diapocarotene-661015840-dioate Brazil Oil [52]Dimethyl-(9Z91015840Z)-661015840-diapocarotene-661015840-dioate Brazil Oil [50]Phytoene Brazil Oil [46]Phytofluene Brazil Oil [46]Geranylgeraniol Brazil Oil [52]Lutein Suriname 196∘C [48]Methyl-(9Z)-101015840-oxo-6101015840-diapocarotene-6-oate Brazil Oil [50]Methyl-(9Z)-61015840-oxo-651015840-diapocarotene-6-oate Brazil Oil [50]Methyl-(9Z)-81015840-oxo-681015840-diapocarotene-6-oate Brazil Oil [50]Methyl-(91015840Z)-apo-61015840-lycopenoate Brazil Oil [46]Methyl-(7Z9Z91015840Z)-apo-61015840-lycopenoate Brazil Oil [55]Methyl-(9Z)-apo-81015840-lycopenoate Brazil Oil [46]Methyl-(all-E)-apo-81015840-lycopenoate Brazil Oil [46]Neurosporene Brazil Oil [46]Norbixin Brazil 300∘C [52]Trans-bixin Jamaica 195∘C [56]Zeaxanthin Suriname 215∘C [48]Source [57]
Many other carotenoids (C19 C22 C24 C25 C30 and C
32)
occur in Bixa orellana but constitute a minor percentage ofthe pigments The major oily constituent of annatto seedsis geranylgeraniol representing 1 of dry seeds Norbixin(Figure 1) is a demethylated derivative of bixin and althoughit is a naturally occurring compound it is almost alwaysreferred to as a saponification product of bixin This is theform used for commercial purposes [62]
Currently more than two dozen substances have beenisolated from the seeds of Bixa orellana Besides bixin andnorbixin other compounds such as isobixin beta-carotenecryptoxanthin lutein zeaxanthin orellin bixein bixol cro-cetin ishwarane ellagic acid salicylic acid threonine tomen-tosic acid tryptophan and phenylalanine have been found inthe seeds of annatto In addition the following compounds intheir respective concentrations are found in these seeds 40to 45 cellulose 35 to 55 sugars 03 to 09 essential oils3 fixed oils 10 to 45 pigments and 13 to 16 proteinsand alpha and beta-carotene as well as tannins and saponins[63 64]
Mercadante et al [50 65] isolated eight apocarotenoidsfromannatto seedsmethyl (7Z 9Z 91015840Z)-apo-61015840-lycopenoatemethyl (9Z)-apo-81015840-lycopenoate methyl 1(all-E)-apo-81015840-lycopenoate methyl (all-E)-8-apo-beta-carotene-81015840-oate
methyl (all-E)-apo-61015840-lycopenoate 6-geranylgeranyl-81015840-methyl-681015840diapocaroten-6-81015840dioate 61015840-geranylgeranyl-61015840-methyl-(9Z)-661015840-diapocaroten-6-61015840-dioate and 6-geranylgeranyl-61015840-methyl-6-61015840-diapocaroten-6-61015840-dioate
More than 100 volatile compounds have been detectedin aqueous and organic extracts where 50 of these havealready been identified (eg bornyl acetateprop-caryophyllenecopaene prop-cubebene (+)-cyclosativene geranyl phenylac-etate 1-heptanetiol 3-methylpyridine 4-methylpyridine 120574-elemene 120573-humulene isoledene 120573-pinene seline-6-en-4-ol120575-selinene (minus)-spathulenol and (+)-ylangene) [66]
Because annatto is a rich source of carotenoids it isof great commercial importance In fact the therapeuticproperties of annatto (eg antioxidant and hypoglycemic)have been attributed to its high levels of carotenoids [67ndash69]Table 2 lists some of these compounds
The pigments in annatto seeds can be extracted bymechanical processes through grinding the seeds and byphysical-chemical methods using solvents or enzymes [46]The solvent extraction can be performed using three basicmethods alkaline extraction (NaOH or KOH solutions)which results in the conversion of bixin to norbixinextraction with oil (soybean corn) and extraction usingorganic solvents (hexane chloroform ethanol acetone or
The Scientific World Journal 5
Bixin (Z-bixin or cis-bixin)
COOH
COOMe
116
(a)
MeOOC 16 1
Isobixin (E-bixin or trans-bixin)
COOH
(b)
COOHHOOC
Norbixin
(c)
OH
Geranylgeraniol
(d)
Figure 1 Chemical structure of some pigments of annatto
propylene glycol) which results in the purest form of pig-ments
Barbosa-Filho et al [49] studied the seeds of four typesof annatto cultivated in Paraıba State Brazil namely ldquocas-caverderdquo (ldquogreen peelrdquo) ldquocascavermelhardquo (ldquored barkrdquo) ldquobicode calangordquo (ldquolizard beakrdquo) and ldquograopretordquo(ldquoblack grainrdquo)with respect to their oil (material extracted with hexane)and solid (material extracted with chloroform) contentsand also pure bixin which was obtained by successiverecrystallization from the chloroform fraction Pure bixinappears as red-purple crystals with a melting point of 196ndash198∘CThe different concentrations found for the oil fractionchloroform extract and bixin are as follows red bark 58lizard beak 51 green peel 49 and black grain 46 Redbark shows the highest yield for both solvent fractions andthe bixin amount is around 1This species has been reportedas the most used in folk medicine On the other hand blackgrain shows negligible amounts of bixin
6 Biological Activity
Table 3 shows data found in 38 studies performed withannatto in 15 different countries in the American countriesTo obtain the extracts and fractions tested several plant partswere used such as leaf root seed shoot and even the wholeplant The data surveyed were classified according to thepharmacological activity tested
Among the twenty-one activities tested those with thelargest number of studies performed were antifungal activity(12) antibacterial activity (12) antimalarial activity (6) andmutagenic activity (3) Cytotoxic activity and toxicity havebeen little studied with three and two studies respectivelyPharmacological activities have been evaluated in animalmodels (22 preclinical studies) human models (1 clinicalstudy) cell cultures (2 studies) and in vitro tests (32 studies)
Antifungal activity has been investigated in one countryin Central America (Guatemala) and in two countries inSouth America (Ecuador and Argentina) using eleven differ-ent fungal strains [70 82 84]
Freixa et al [82] conducted a study in Ecuador to assessthe antifungal activity of extracts from the dried leaves of
the annatto tree in response to 7 fungi species obtainingsatisfactory antifungal activity against Trichophyton menta-grophytes trains In Guatemala three different strains wereused to evaluate antifungal activity with no satisfactoryactivity being observed [84]
The extracts of annatto leaves have been evaluated forantibacterial activity against 8 different bacterial strains(Bacillus subtilis Escherichia coli Micrococcus luteus Pseu-domonas aeruginosa Staphylococcus aureus Salmonella typhiShigella dysenteriae and Staphylococcus epidermidis) show-ing no activity
Antimalarial activity has been determined against Plas-modium gallinaceum Plasmodium lophurae andPlasmodiumberghei Although the studies conducted previously in theUnited States did not show significant results [92] Valdes etal (2011) reported a moderate activity of the seed extracts ofBixa orellana against Plasmodium berghei and falciparum
7 Mutagenic and Cytotoxic Activities
No significant effect was observed when extracts of annattoseeds were tested for mutagenic activity in studies performedin the United States and Brazil [67 93]
Extracts obtained from annatto seeds and leaves havebeen tested in cell cultures and the brine shrimp assayrespectively and have been found to lack cytotoxicity ineither model used These experiments were carried out inGuatemala and the Dominican Republic [83 89]
On the other hand a study performed in Cuba with 10medicinal plants that were active in inhibiting human lungcarcinoma cell growth showed that the ethanolic extract ofBixa orellana presented cytotoxicity at concentrations below100 120583gmL [81]
8 Toxicological Activities
Currently concerns about the effect of synthetic dyes onhuman health are incontestable making people increasinglychoose those of natural origin believing that they are devoidof toxic effects This is not entirely true because even amedication from a natural source can be a poison depending
6 The Scientific World Journal
Table3Biologicalactiv
ities
ofextractsof
annatto
inAmerican
coun
tries
Cou
ntry
biologicalactiv
ityPartused
Type
ofextract
Organism
teste
dMod
elteste
dDoseu
sed
Activ
ityRe
ferences
Argentin
aAntibacteria
lLE
EtOH
Bacillussubtilis
Invitro
5mgmL
Inactiv
e[70]
Escherich
iacoli
Invitro
5mgmL
Inactiv
e[70]
Micrococcusluteus
Invitro
5mgmL
Inactiv
e[70]
Pseudomonas
aeruginosa
Invitro
5mgmL
Inactiv
e[70]
Staphylococcus
aureus
Invitro
5mgmL
Inactiv
e[70]
Antifu
ngal
LEEtOH
Aspergillus
niger
Invitro
5mgmL
Inactiv
e[70]
Cand
idaalbicans
Invitro
5mgmL
Inactiv
e[70]
Antivira
lSE
EtOH
VirusH
erpessim
plex
1Cell
cultu
re078
mgmL
Inactiv
e[71]
Insecticidal
AP
MeO
HInsect
Sitophilu
soryzae
5Inactiv
e[71]
Brazil
Antim
alarial
SECH
Cl3
Mou
sePlasmodium
berghei
100m
gkg
Inactiv
e[26]
Antioxidant
SEEtOH
Invitro
DPP
Hassay
01g
Lminus1
Activ
e[6]
Insectrepellent
SEPetr
eth
Ham
ster
Lutzom
yialongipalpis
1gL
Activ
e[72]
SEEtOH
Mosqu
itoAe
desa
egypti
182mgmL
Activ
e[6]
Molluscicidal
SEEtOH
Con
chBiom
phalariagla
brata
10000
ppm
Inactiv
e[73]
Mutagenic
Powder
Mou
seBo
nemarrowcells
10670
ppm
Inactiv
e[67]
Toxicity
SEPo
wder
Rat
Invivo
500m
gkg
Inactiv
e[74]
Antileish
manial
LERO
EtOH
Leish
maniaam
azonensis
Invitro
012ndash25mgmL
Activ
e[75]
Antileish
manial
SEOE
Leish
maniaam
azonensis
Invitro
10501005001000120583gmL
Activ
e[76]
Hyperlip
idem
iaSE
H2O
Mou
seIn
vitro
400and800m
gkg
Activ
e[77]
Colom
bia
Snakebite
LEEtOH
Mou
seBo
throps
atrox
LD50gt260120583
ganim
alAc
tive
[29]
CostaRica
Anti-infl
ammatory
ROEtOH
Rat
Pawedem
acarrageenan
100m
gkg
Inactiv
e[78]
Cuba Positiveino
tropice
ffect
AP
H2O
Guineap
igIsolated
atriu
m320120583
LInactiv
e[79]
Antim
alarial
SEPlasmodium
gallina
ceum
falciparum
Invivoin
vitro
500m
gkg
Activ
e[80]
Cytotoxic
SEEtOH
Tumor
cells
Invitro
39ndash
250m
gmL
Activ
e[81]
Ecuado
rAntifu
ngal
LEMeO
HAspergillus
niger
Invitro
10mgdisk
Inactiv
e[82]
Cand
idaalbicans
Invitro
10mgdisk
Inactiv
e[82]
Cryptococcus
neoforman
sIn
vitro
10mgdisk
Inactiv
e[82]
Fusariu
moxysporum
Invitro
10mgdisk
Inactiv
e[82]
Neurospora
crassa
Invitro
10mgdisk
Inactiv
e[82]
Penicilliu
mpurpurogenum
Invitro
10mgdisk
Inactiv
e[82]
Trich
ophytonmentagrophytes
Invitro
10mgdisk
Activ
e[82]
The Scientific World Journal 7
Table3Con
tinued
Cou
ntry
biologicalactiv
ityPartused
Type
ofextract
Organism
teste
dMod
elteste
dDoseu
sed
Activ
ityRe
ferences
Guatemala
Antibacteria
lLE
Vario
usEscherich
iacoli
Invitro
50120583Ldisk
Inactiv
e[83]
Pseudomonas
aeruginosa
Invitro
MICgt10mgmL
Inactiv
e[83]
Salm
onellatyphi
Invitro
MICgt10mgmL
Inactiv
e[83]
Shigelladysenteriae
Invitro
50120583L
Inactiv
e[83]
Staphylococcus
aureus
Invitro
MICgt10mgmL
Inactiv
e[83]
Antifu
ngal
LEH
2OAspergillus
flavus
Invitro
MICgt10mgmL
Inactiv
e[84]
Cand
idaalbicans
Invitro
MICgt10mgmL
Inactiv
e[84]
Microsporum
gypseum
Invitro
MICgt10mgmL
Inactiv
e[84]
Antigon
orrheal
LEEtOH
Neisseriagonorrhea
Invitro
50120583Ldisk
Activ
e[32]
Antitrypanosom
alLE
EtOH
Trypanosom
acruzi
Invitro
MICgt1m
gmL
Inactiv
e[83]
Cytotoxic
LEH
2OCr
ustacean
Artemiasalin
aLC
50gt10
00pp
mInactiv
e[83]
Inhibof
plateletaggregation
SE
Invitro
Thrombinaggregation
IC50
0795m
gmL
Inactiv
e[35]
Haw
aii
Con
traceptiv
eRO
Mou
se
02m
Lanim
alInactiv
e[85]
Jamaica
Hypoglycemic
SECH
Cl3
Dog
1gAc
tive
[39]
H2O
Dog
200m
Lanim
alAc
tive
[39]
Antioxidant
SEEtOH
Invitro
Invitro
025
and25120583
gmL
Activ
e[86]
Mexico
Allergenic
SEOil
Hum
an25120583L
person
Activ
e[87]
Paragu
ayInsecticidal
SEPetr
ether
Insect
Rhodnius
negle
ctus
50120583g
Inactiv
e[42]
Puerto
Rico
Molluscicidal
TPH
2OCon
chLymna
eacubensis
LD100gt1M
ppm
Inactiv
e[88]
Dom
inican
Repu
blic
Cytotoxic
SEEtOH
Cellculture
Molt4
cells
200120583
gmL
Inactiv
e[89]
Trinidad
andTo
bago
Antibacteria
lSE
EtOAc
Escherich
iacoli
Invitro
1000120583gmL
Inactiv
e[90]
Pseudomonas
aeruginosa
Invitro
1000120583gmL
Inactiv
e[90]
USA A
nticon
vulsa
ntRA
EtOH
Mou
seSeizureselectroshock
100m
gkg
Inactiv
e[91]
Rat
Seizurespentylenetetrazole
400m
gkg
Inactiv
e[91]
Antim
alarial
SECH
Cl3
Chicken
Plasmodium
gallina
ceum
388m
gkg
Inactiv
e[92]
Mutagenic
SEMeO
HSalm
onellatyphim
urium
100m
gplaque
Inactiv
e[93]
H2O
Invitro
Placentaltroph
oblasts
100m
gplaque
Inactiv
e[93]
Hypotensiv
eRA
EtOH
Rat
50mgkg
Activ
e[93]
Toxicity
RAH
2OMou
seLD
50gt700m
gkg
Inactiv
e[92]
LEleafAP
aeria
lpartTP
totalplantRO
roo
tSE
seedno
tgivenLD5050
lethaldo
seIC5
0concentrationthatinhibits50of
thee
ffectM
ICm
inim
uminhibitory
concentration
8 The Scientific World Journal
on the dose that is administered The failure to require in-depth data related to toxicological and chemical analysesfor the registration of food additives derived from naturalsources [67 74] certainly makes the information aboutpossible unwanted effects andor pharmacological activitiesresulting from their use much rarer than expected in view ofthe importance of the topic In Brazil the use of annatto is sowidespread that its safety is not even questioned
Paumgartten et al [91] evaluated the toxicity of annattoextracts in rats Doses up to 500mgkg body weightdaywere introduced directly into the stomach of pregnant ratsto evaluate the effect on the mother and fetus and noadverse effects were found for either The annatto extract didnot induce an increase in the incidence of visible externalvisceral or skeletal anomalies in the fetuses Therefore thestudy suggested that the annatto extract was not toxic to ratsnor was it embryotoxic Studies performed in Brazil by Alvesde Lima et al [67] where extracts of annatto weremixed withthe food of male rats showed that the concentrations testedhad no mutagenic or antimutagenic activity in their bonemarrow cells A parallel toxicity study conducted byHagiwaraet al [74] showed that 01 annatto extract administered forthirteen weeks in the feed of male and female rats did notshow any adverse effects However when higher doses wereadministered (03 and 09) the authors noticed an increasein liver weight as well as changes in blood chemistriesincluding increase in alkaline phosphatase phospholipidsand total protein as well as albumin and albuminglobulinratio
Hagiwara et al [74] also evaluated extracts of annattofor liver carcinogenicity in rats and found no evidence ofliver tumors even when given to animals at a high dose of200mgkg body weightday compared to an acceptable doseof 00 to 0065mgkgday thus indicating that the dangerof a hepatocarcinogenic effect in humans may be absent ornegligible
A toxicity test was performedwith extracts obtained fromboth plant seeds and shoots and no significant effect wasobserved The experiments were performed in the UnitedStates using mice as the animal model and it was found thatthe LD50 was greater than 700mgkg [92]
9 Correlation between the BiologicalActivities Phytochemistry and theTraditional Uses of Bixa orellana
Table 1 shows that many of the traditional uses of Bixaorellana are the same in several countries of South andCentral America which suggests its effectiveness as a ther-apeutic agent Extracts of Bixa orellana showed biologicalactivities such as antioxidant hypotensive molluscicideand antimalarial against A549 cells for carcinoma of thelung allergy hypoglycemic antifungal antioxidant insectrepellent antigonococcal and antivenom serum and some ofthem are in accordance with the traditional use for examplein Brazil it is used to extract the seeds with purpose repellentinsecticide and antimalaria and scientific studies in the samecountrywith the Lutzomyia longipalpis insect repellent action
and prove a study in Cuba proved the pharmacological actionfor antimalarial activity when tested against Plasmodiumberghei Some of them are in accordance with the traditionaluse for example seed extracts have been used in Brazil andCuba as insect repellent and antimalarial Antioxidant andinsect repellent activities can be attributed to the carotenoidsand the essential and fixed oils respectively
Despite the previous reports about the presence of com-ponents with anti-inflammatory properties such as salicylicacid lutein polyphenols and tannins this activity has not yetbeen proven for Bixa orellana extracts Similarly the plantrsquosessential and fixed oils have shown antibacterial propertiesalthough this activity has not been proven too
In general the data obtained in this review do not allowcorrelations between the biologic activities tested in vitro or invivo with the compounds identified in this species Howevertaking into account the related activities such as the antipara-sitic effect and the lack of mutagenic and cytotoxicity activityit is possible to consider Bixa orellana as a potential source forthe development of phytopharmaceutical products
In conclusion the studies discussed in this review repre-sent a rich database around the Bixa orellana activities andits potential uses which evokes the feasibility of phytophar-maceuticals to treat some diseases whenever an antioxidanthypotensor or hypoglycemiant activity is necessary
Although the commercial exploitation of this species iswell established there are very few studies on its pharma-cological effects Considering the need for developing a safeand effective product more studies should be performed inorder to confirm other biological activities supported by thepopular uses of Bixa orellana
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors are grateful to CNPqPRONEXFAPESQ andCAPES for financial support and to the NAPRALERTDatabase of the University of Illinois USA for the literatureon Bixa orellana A Leyva helped in editing the Englishlanguage of the paper
References
[1] M B Perecin O A Bovi and N B Maia ldquoPesquisa complantas aromaticas medicinais corantes o papel do InstitutoAgronomicordquo O Agronomico vol 54 pp 21ndash24 2002
[2] M E A Elias G Schroth J L V Macedo M S S Motaand S A DrsquoAngelo ldquoMineral nutrition growth and yields ofannatto trees (Bixa orellana) in agroforestry on an AmazonianFerralsolrdquo Experimental Agriculture vol 38 no 3 pp 277ndash2892002
[3] A R R Bastos J G Carvalho R P Assis and A B C FilholdquoMarcha de absorcao de nutrientes em urucum ( Bixa orellanaL) tipo cultivado piave vermelha em fase de viveirordquoCerne vol5 pp 76ndash85 1999
The Scientific World Journal 9
[4] E PThomasM Colvin S B Rosen C Zuccarini and S PetzerldquoHIV prevalence study and costing analysis undertaken for thedevelopment of an HIVAIDS workplace strategy for buffalocity municipalityrdquo Tech Rep Medical Research Council Buf-falo NY USA 2005
[5] C F Franco ldquoO Agronegocio do urucum na regiao Nordesterdquo 1Reuniao Nacional da Cadeia Produtiva de Urucum CD-Rom2007
[6] A Giorgi P De Marinis G Granelli L M Chiesa and SPanseri ldquoSecondary metabolite profile antioxidant capacityand mosquito repellent activity of Bixa orellana from BrazilianAmazon regionrdquo Journal of Chemistry vol 2013 Article ID409826 10 pages 2013
[7] J S Silva M D Moura R A G Oliveira M F F Dinizand J M Barbosa-Filho ldquoNatural product inhibitors of ovarianneoplasiardquo Phytomedicine vol 10 no 2-3 pp 221ndash232 2003
[8] F C F Sousa C T V Melo C O M Cito et al ldquoPlantasmedicinais e seus constituintes bioativos uma revisao dabioatividade e potenciais benefıcios nos disturbios da ansiedadeem modelos animaisrdquo Revista Brasileira de Farmacognosia vol18 pp 642ndash654 2008
[9] L J Quintans Jr J R G S Almeida J T Lima et al ldquoPlantswith anticonvulsant propertiesmdasha reviewrdquo Revista Brasileira deFarmacognosia vol 18 pp 798ndash819 2008
[10] HD S Falcao J A Leite JM Barbosa-Filho et al ldquoGastric andduodenal antiulcer activity of alkaloids a reviewrdquoMolecules vol13 no 12 pp 3198ndash3223 2008
[11] H S Falcao I R Mariath M F F M Diniz L M Batista andJ M Barbosa-Filho ldquoPlants of the American continent withantiulcer activityrdquo Phytomedicine vol 15 no 1-2 pp 132ndash1462008
[12] I R Mariath H D S Falcao J M Barbosa-Filho et al ldquoPlantsof the American continent with antimalarial activityrdquo RevistaBrasileira de Farmacognosia vol 19 no 1 pp 158ndash192 2009
[13] J E R Hon P M Soares C L Melo et al ldquoAtividadefarmacologica da monocrotalina isolada de plantas do generoCrotalariardquo Revista Brasileira de Farmacognosia vol 20 pp453ndash458 2010
[14] R N Almeida D S Navarro and J M Barbosa-Filho ldquoPlantswith central analgesic activityrdquo Phytomedicine vol 8 no 4 pp310ndash322 2001
[15] N Z T Jesus H S Falcao I F Gomes et al ldquoTanninspeptic ulcers and related mechanismsrdquo International Journal ofMolecular Sciences vol 13 no 3 pp 3203ndash3228 2012
[16] L G Rocha J R G S Almeida R O Macedo and J MBarbosa-Filho ldquoA review of natural products with antileishma-nial activityrdquo Phytomedicine vol 12 no 6-7 pp 514ndash535 2005
[17] G R M Lima C A Montenegro C L F Almeida PF Athayde-Filho J M Barbosa-Filho and L M BatistaldquoDatabase survey of anti-inflammatory plants in South Amer-ica a reviewrdquo International Journal ofMolecular Sciences vol 12no 4 pp 2692ndash2749 2011
[18] K S De Lira Mota G E N Dias M E F Pinto et alldquoFlavonoids with gastroprotective activityrdquo Molecules vol 14no 3 pp 979ndash1012 2009
[19] A L Souto J F Tavares M S da Silva M F F M de Diniz P Fde Athayde-Filho and J M Barbosa Filho ldquoAnti-inflammatoryactivity of alkaloids an update from 2000 to 2010rdquo Moleculesvol 16 no 10 pp 8515ndash8534 2011
[20] F L Silva D C H Fischer J F Tavares M S Silva P Fde Athayde-Filho and J M Barbosa-Filho ldquoCompilation of
secondary metabolites from Bidens pilosa LrdquoMolecules vol 16no 2 pp 1070ndash1102 2011
[21] J R Filho H de Sousa Falcao L M Batista J M B Filho andM R Piuvezam ldquoEffects of plant extracts on HIV-1 proteaserdquoCurrent HIV Research vol 8 no 7 pp 531ndash544 2010
[22] JM Barbosa-Filho A A Alencar X P Nunes et al ldquoSources ofalpha- beta- gamma- delta- and epsilon-carotenes a twentiethcentury reviewrdquo Revista Brasileirta de Farmacogn vol 18 no 1pp 135ndash154 2008
[23] S N S Silva C L F Amaral and T N H Reboucas ldquoAdoptionof conservation practices on farm and selection of varieties byproducers of annatto in the city of Vitoria da Conquista-BArdquoRevista Brasileira de Agroecologica vol 5 pp 106ndash113 2010
[24] A L Bandoni M E Mendiondo R V D Rondina and J DCoussio ldquoSurvey of Argentine medicinal plants I Folklore andphytochemical screeningrdquo Lloydia vol 35 no 1ndash4 pp 69ndash801972
[25] G H Garcia R Campos R A de Torres et al ldquoAntiherpeticactivity of some Argentine medicinal plantsrdquo Fitoterapia vol61 no 6 pp 542ndash546 1990
[26] M G L Brandao T S M Grandi E M M Rocha D RSawyer and A U Krettli ldquoSurvey of medicinal plants used asantimalarials in the Amazonrdquo Journal of Ethnopharmacologyvol 36 no 2 pp 175ndash182 1992
[27] M P Correa Dicionario das Plantas Uteis do Brasil e dasExoticas Cultivadas vol 4 Ministerio da AgriculturaIBDF Riode Janeiro Brasil 1978
[28] G S Hirschmann and A R de Arias ldquoA survey of medicinalplants of minas gerais Brazilrdquo Journal of Ethnopharmacologyvol 29 no 2 pp 159ndash172 1990
[29] R Otero R Fonnegra S L Jimenez et al ldquoSnakebites andethnobotany in the northwest region of Colombia Part Itraditional use of plantsrdquo Journal of Ethnopharmacology vol 71no 3 pp 493ndash504 2000
[30] H Garcia-Barriga Flora Medicinal de Colombia vol 2 Univer-sidad Nacional Bogota Colombia 1975
[31] J T Roig y Mesa Plantas Medicinales Aromaticas o Venenosasde Cuba Ministerio de Agricultura Havana Cuba 1945
[32] A Caceres H Menendez E Mendez et al ldquoAntigonorrhoealactivity of plants used inGuatemala for the treatment of sexuallytransmitted diseasesrdquo Journal of Ethnopharmacology vol 48no 2 pp 85ndash88 1995
[33] J A Duke and R V Martinez Amazonian EthnobotanicalDictionary CRC Press Boca Raton Fla USA 1994
[34] V R Ramirez L J Mostacero A E Garcia et al VegetalesEmpleados enMedicina Tradicional Norperuana Banco Agrariodel Peru Universidad Nacional de Trujillo Trujillo Peru 1988
[35] R Villar J M Calleja C Morales and A Caceres ldquoScreeningof 17 Guatemalan medicinal plants for platelet antiaggregantactivityrdquo Phytotherapy Research vol 11 pp 441ndash445 1997
[36] L M Giron V Freire A Alonzo and A Caceres ldquoEthnob-otanical survey of the medicinal flora used by the Caribs ofGuatemalardquo Journal of Ethnopharmacology vol 34 no 2-3 pp173ndash187 1991
[37] D L Lentz ldquoMedicinal and other economic plants of the PayaofHondurasrdquo Economic Botany vol 47 no 4 pp 358ndash370 1993
[38] D L Lentz A M Clark C D Hufford et al ldquoAntimi-crobial properties of Honduran medicinal plantsrdquo Journal ofEthnopharmacology vol 63 no 3 pp 253ndash263 1998
[39] E Y Morrison and M E West ldquoThe effect of Bixa orellana(Annatto) on blood sugar levels in the anaesthetized dogrdquoWestIndian Medical Journal vol 34 no 1 pp 38ndash42 1985
10 The Scientific World Journal
[40] F G Coe and G J Anderson ldquoScreening of medicinal plantsused by the Garıfuna of eastern Nicaragua for bioactive com-poundsrdquo Journal of Ethnopharmacology vol 53 no 1 pp 29ndash501996
[41] B Barrett ldquoMedicinal plants of Nicaraguarsquos Atlantic CoastrdquoEconomic Botany vol 48 no 1 pp 8ndash20 1994
[42] G Schmeda-Hirschmann and A R de Arias ldquoA screeningmethod for natural products on triatomine bugsrdquo PhytotherapyResearch vol 6 no 2 pp 68ndash73 1992
[43] G E Simpson ldquoFolk medicine in Trinidadrdquo The Journal ofAmerican Folklore vol 75 no 298 pp 326ndash340 1962
[44] D Mahabir and M C Gulliford ldquoUse of medicinal plants fordiabetes in Trinidad and Tobagordquo Revista Panamericana deSalud Publica vol 1 no 3 pp 174ndash179 1997
[45] E S Ayensu ldquoMedicinal plants of theWest IndiesrdquoUnpublishedManuscript 1978
[46] A Z Mercadante A Steck D Rodriguez-Amaya H Pfanderand G Britton ldquoIsolation of methyl 91015840Z-APO-61015840-lycopenoatefrom Bixa Orellanardquo Phytochemistry vol 41 no 4 pp 1201ndash1203 1996
[47] E Angelucci H K Arima E A Kumagai and I AnnattoldquoPreliminary data of the chemical compositionrdquo Coletanea doInstituto de Tecnologia de Alimentos vol 11 pp 89ndash96 1980
[48] A S L Tirimanna ldquoStudy of the carotenoid pigments of Bixaorellana L Seeds by thin layer chromatographyrdquo MikrochimicaActa vol 76 no 1-2 pp 11ndash16 1981
[49] J M Barbosa-Filho R N Silva-Filho B F Lira et al ldquoTeor debixina em quatro variedades de Bixa orellana L cultivadas naParaıbardquo Revista Brasileira de Farmacognosia vol 7-8 pp 41ndash47 1998
[50] A Z Mercadante A Steck and H Pfander ldquoIsolation andstructure elucidation of minor carotenoids from annatto (Bixaorellana L) seedsrdquo Phytochemistry vol 46 no 8 pp 1379ndash13831997
[51] C Prentice-Hernandez and O Rusig ldquoAnnatto (Bixa orellanaL) extract obtained using ethyl alcohol as a solventrdquo Arquivosde Biologia e Tecnologia vol 35 pp 63ndash74 1992
[52] A Z Mercadante ldquoComposition of carotenoids from annattordquoACS Symposium Series vol 775 pp 92ndash101 2001
[53] M J Scotter L A Wilson G P Appleton and L CastleldquoAnalysis of Annatto (Bixa orellana) Food Coloring Formula-tions 1 Determination of Coloring Components and ColoredThermal Degradation Products by High-Performance LiquidChromatography with Photodiode Array Detectionrdquo Journal ofAgricultural and Food Chemistry vol 46 no 3 pp 1031ndash10381998
[54] A J Degnan J H von Elbe and R W Hartel ldquoExtraction ofannatto seed pigment by supercritical carbon dioxiderdquo Journalof Food Science vol 56 pp 1655ndash1659 1991
[55] A ZMercadante A Steck andH Pfander ldquoIsolation and iden-tification of new apocarotenoids from annatto (Bixa orellana)seedsrdquo Journal of Agricultural and Food Chemistry vol 45 no4 pp 1050ndash1054 1997
[56] S G Anderson M G Nair A Chandra and E MorrisonldquoSupercritical fluid carbon dioxide extraction of annatto seedsand quantification of trans-bixin by high pressure liquid chro-matographyrdquo Phytochemical Analysis vol 8 pp 247ndash249 1997
[57] J M Barbosa-Filho Bixa orellana Retrospectiva de usos pop-ulares atividades biologicas fitoquımica e emprego na fito-cosmetica no continente americano Simposio Brasileiro doUrucummdashSIMBRAU Joao Pessoa Brazil 2006
[58] J Revilla Plantas da Amazonia Oportunidades Economicas eSustentaveis Manaus Programa de Desenvolvimento Empre-sarial e Tecnologico 2nd edition 2001
[59] F Oliveira G Akisue and M K Akisue FarmacognosiaAtheneu Sao Paulo Brazil 1996
[60] J Alonso Tratado de Fitofarmacos y Nutraceuticos CorpusRosario Argentina 2004
[61] C O Franco E G Fabri M Barreiro Neto M H Manfiolli MN C Harder and N C Rucker Urucum Sistema de Producaopara o Brasil Emepa-Pb Apta Joao Pessoa Brazil 2008
[62] P A Venugopalan G A Giridhar and A G RavishankarldquoFood Ethanobotanical and diversified applications of Bixaorellana L a scope for its improvement through biotechnolog-ical mediationrdquo Indian Journal of Fundamental and Applied LifeSciences vol 1 pp 9ndash31 2011
[63] L Taylor Herbal Secrets of the Rainforest Sage Press RocklinCalif USA 2nd edition 2002
[64] J S Oliveira Caracterizacao Extracao e Purificacao por Cro-matografia de Compostos de Urucum (Bixa orellana L) [tesisdoctoral en Ingenierıa Quımic] Universidade Federal de SantaCatarina Florianopolis Brazil 2005
[65] A Z Mercadante A Steck and H Pfander ldquoThree minorcarotenoids from annatto (Bixa orellana) seedsrdquo Phytochem-istry vol 52 no 1 pp 135ndash139 1999
[66] V Galindo-Cuspinera M B Lubran and S A Rankin ldquoCom-parison of volatile compounds in water- and oil-soluble annatto(Bixa orellana L) extractsrdquo Journal of Agricultural and FoodChemistry vol 50 no 7 pp 2010ndash2015 2002
[67] R O Alves de Lima L Azevedo L R Ribeiro and D M FSalvadori ldquoStudy on the mutagenicity and antimutagenicity ofa natural food colour (annatto) in mouse bone marrow cellsrdquoFood and Chemical Toxicology vol 41 no 2 pp 189ndash192 2003
[68] L R P Lima T T Oliveira T J Nagem et al ldquoBixina norbixinae quercetina e seus efeitos no metabolismo lipıdico de coelhosrdquoBrazilian Journal of Veterinary Research andAnimal Science vol38 pp 196ndash200 2001
[69] J D Fontana S V Mendes D S Persike L F Peracetta andM Passos ldquoCarotenoides cores atraentes e acao biologicardquoBiotecnologia Ciencia amp Desenvolvimento vol 2 p 13 2000
[70] C A Penna M Radice G O Gutkind et al ldquoAntibacterial andantifungal activities of some Argentinean plantsrdquo Fitoterapiavol 65 no 2 pp 172ndash174 1994
[71] A M Broussalis G E Ferraro V S Martino R Pinzon J DCoussio and J C Alvarez ldquoArgentine plants as potential sourceof insecticidal compoundsrdquo Journal of Ethnopharmacology vol67 no 2 pp 219ndash223 1999
[72] A Rojas de Arias G Schmeda-Hirschmann and A FalcaoldquoFeeding deterrency and insecticidal effects of plant extracts onLutzomyia longipalpisrdquo Phytotherapy Research vol 6 no 2 pp64ndash67 1992
[73] M S Pinheiro and M Z Rouquayrol ldquoMolluscicidal activityof plants from Northeast Brazilrdquo Revista Brasileira de PesquisasMedicas e Biologicas vol 7 pp 389ndash394 1974
[74] A Hagiwara N Imai T Ichihara et al ldquoA thirteen-week oraltoxicity study of annatto extract (norbixin) a natural food colorextracted from the seed coat of annatto (Bixa orellana L) inSprague-Dawley ratsrdquoFood andChemical Toxicology vol 41 no8 pp 1157ndash1164 2003
[75] C R Almeida R B Silva M J Marques and J K ChavascoldquoEvaluation of antiparasitic activity of hydroethanolic extractsfrom root stem and leaf of Bixa orellana L on Leishmania
The Scientific World Journal 11
amazonensis samplesrdquo Revista da Universidade Vale do RioVerde vol 10 no 2 pp 384ndash391 2012
[76] M V Lopes V C Desoti A D O Caleare T Ueda-NakamuraS O Silva and C V Nakamura ldquoMitochondria superoxideanion production contributes to geranylgeraniol-induced deathin leishmania amazonensisrdquo Evidence-Based Complementaryand Alternative Medicine vol 2012 Article ID 298320 9 pages2012
[77] J M Ferreira D F Sousa M B Dantas et al ldquoEffects of BixaorellanaL seeds onhyperlipidemiardquoPhytotherapyResearch vol27 no 1 pp 144ndash147 2013
[78] P S BenoitHH S FongGH Svoboda andN R FarnsworthldquoBiological and phytochemical evaluation of plants XIV Anti-inflammatory evaluation of 163 species of plantsrdquo Lloydia vol39 no 2-3 pp 160ndash171 1976
[79] D Carabajal A Casaco L Arruzazabala R Gonzalez andV Fuentes ldquoPharmacological screening of plant decoctionscommonly used in Cuban folk medicinerdquo Journal of Ethnophar-macology vol 33 no 1-2 pp 21ndash24 1991
[80] A F C Valdes J M Martınez D A Rodrıguez R S Lizamaand Y G Gaiten ldquoActividad antimalarica de un extractohidroalcoholico de Bixa orellanaLrdquo Revista Cubana de Medic-ina Tropical vol 63 pp 181ndash185 2011
[81] A D Garcıa H R Sanchez and R S Lizama ldquoCitotoxicidadde extractos de plantas medicinales sobre la lınea celularde carcinoma de pulmon humano A549rdquo Revista Cubana deFarmacia vol 45 pp 101ndash108 2011
[82] B Freixa R Vila L Vargas N Lozano T Adzet and SCanigueral ldquoScreening for antifungal activity of nineteen LatinAmerican plantsrdquo Phytotherapy Research vol 12 no 6 pp 427ndash430 1998
[83] A Caceres B Lopez S Gonzalez I Berger I Tada and JMaki ldquoPlants used in Guatemala for the treatment of pro-tozoal infections I Screening of activity to bacteria fungiand American trypanosomes of 13 native plantsrdquo Journal ofEthnopharmacology vol 62 no 3 pp 195ndash202 1998
[84] A Caceres O Cano B Samayoa and L Aguilar ldquoPlants usedin Guatemala for the treatment of gastrointestinal disorders1 Screening of 84 plants against enterobacteriardquo Journal ofEthnopharmacology vol 30 no 1 pp 55ndash73 1990
[85] A S Matsui S Hoskin M Kashiwagi et al ldquoA survey ofnatural products from Hawaii and other areas of the Pacificfor an antifertility effect in micerdquo Internationale Zeitschrift furKlinische PharmakologieTherapie und Toxikologie vol 5 no 1pp 65ndash69 1971
[86] M Abayomi A S Adebayo D Bennett R Porter and JS Campbell ldquoIn vitro antioxidant activity of Bixa orellana(Annatto) seed extractrdquo Journal of Applied PharmaceuticalScience vol 4 no 2 pp 101ndash106 2014
[87] NW Dunham and K R Allard ldquoA preliminary pharmacologicinvestigation of the roots of Bixa orellanardquo Journal of theAmerican Pharmacist Associantion vol 49 pp 218ndash219 1960
[88] F RMedina andRWoodbury ldquoTerrestrial plantsmolluscicidalto lymnaeid hosts of Fasciliasis hepatica in Puerto Ricordquo Journalof Agricultura of the University of Puerto Rico vol 63 pp 366ndash376 1979
[89] B Weniger Y Jiang A Oulad-Ali L Italiano J P Beck and RAnton ldquoBiological effects of bixin and Bixa orellana extracts onlymphoid cells in culturerdquo Planta Medica vol 59 no 7 articleA680 1993
[90] CM Chariandy C E Seaforth R H Phelps G V Pollard andB P S Khambay ldquoScreening of medicinal plants from Trinidad
and Tobago for antimicrobial and insecticidal propertiesrdquoJournal of Ethnopharmacology vol 64 no 3 pp 265ndash270 1999
[91] F J R Paumgartten R R Carvalho I B Araujo et alldquoEvaluation of the developmental toxicity of annatto in the ratrdquoFood and Chemical Toxicology vol 40 no 11 pp 1595ndash16012002
[92] C F Spencer F R Koniuszy E F Rogers et al ldquoSurvey of plantsfor antimalarial activityrdquo Lloydia vol 10 no 3 pp 145ndash174 1947
[93] H Mikkelsen J C Larsen and F Tarding ldquoHypersensitivityreactions to food colours with special reference to the naturalcolour annatto extract (butter colour)rdquo Toxicological Aspects ofFood Safety vol 1 pp 141ndash143 1978
Submit your manuscripts athttpwwwhindawicom
PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom
Volume 2014
ToxinsJournal of
VaccinesJournal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
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AntibioticsInternational Journal of
ToxicologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Drug DeliveryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in Pharmacological Sciences
Tropical MedicineJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
AddictionJournal of
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BioMed Research International
Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Autoimmune Diseases
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Anesthesiology Research and Practice
ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Pharmaceutics
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
The Scientific World Journal 5
Bixin (Z-bixin or cis-bixin)
COOH
COOMe
116
(a)
MeOOC 16 1
Isobixin (E-bixin or trans-bixin)
COOH
(b)
COOHHOOC
Norbixin
(c)
OH
Geranylgeraniol
(d)
Figure 1 Chemical structure of some pigments of annatto
propylene glycol) which results in the purest form of pig-ments
Barbosa-Filho et al [49] studied the seeds of four typesof annatto cultivated in Paraıba State Brazil namely ldquocas-caverderdquo (ldquogreen peelrdquo) ldquocascavermelhardquo (ldquored barkrdquo) ldquobicode calangordquo (ldquolizard beakrdquo) and ldquograopretordquo(ldquoblack grainrdquo)with respect to their oil (material extracted with hexane)and solid (material extracted with chloroform) contentsand also pure bixin which was obtained by successiverecrystallization from the chloroform fraction Pure bixinappears as red-purple crystals with a melting point of 196ndash198∘CThe different concentrations found for the oil fractionchloroform extract and bixin are as follows red bark 58lizard beak 51 green peel 49 and black grain 46 Redbark shows the highest yield for both solvent fractions andthe bixin amount is around 1This species has been reportedas the most used in folk medicine On the other hand blackgrain shows negligible amounts of bixin
6 Biological Activity
Table 3 shows data found in 38 studies performed withannatto in 15 different countries in the American countriesTo obtain the extracts and fractions tested several plant partswere used such as leaf root seed shoot and even the wholeplant The data surveyed were classified according to thepharmacological activity tested
Among the twenty-one activities tested those with thelargest number of studies performed were antifungal activity(12) antibacterial activity (12) antimalarial activity (6) andmutagenic activity (3) Cytotoxic activity and toxicity havebeen little studied with three and two studies respectivelyPharmacological activities have been evaluated in animalmodels (22 preclinical studies) human models (1 clinicalstudy) cell cultures (2 studies) and in vitro tests (32 studies)
Antifungal activity has been investigated in one countryin Central America (Guatemala) and in two countries inSouth America (Ecuador and Argentina) using eleven differ-ent fungal strains [70 82 84]
Freixa et al [82] conducted a study in Ecuador to assessthe antifungal activity of extracts from the dried leaves of
the annatto tree in response to 7 fungi species obtainingsatisfactory antifungal activity against Trichophyton menta-grophytes trains In Guatemala three different strains wereused to evaluate antifungal activity with no satisfactoryactivity being observed [84]
The extracts of annatto leaves have been evaluated forantibacterial activity against 8 different bacterial strains(Bacillus subtilis Escherichia coli Micrococcus luteus Pseu-domonas aeruginosa Staphylococcus aureus Salmonella typhiShigella dysenteriae and Staphylococcus epidermidis) show-ing no activity
Antimalarial activity has been determined against Plas-modium gallinaceum Plasmodium lophurae andPlasmodiumberghei Although the studies conducted previously in theUnited States did not show significant results [92] Valdes etal (2011) reported a moderate activity of the seed extracts ofBixa orellana against Plasmodium berghei and falciparum
7 Mutagenic and Cytotoxic Activities
No significant effect was observed when extracts of annattoseeds were tested for mutagenic activity in studies performedin the United States and Brazil [67 93]
Extracts obtained from annatto seeds and leaves havebeen tested in cell cultures and the brine shrimp assayrespectively and have been found to lack cytotoxicity ineither model used These experiments were carried out inGuatemala and the Dominican Republic [83 89]
On the other hand a study performed in Cuba with 10medicinal plants that were active in inhibiting human lungcarcinoma cell growth showed that the ethanolic extract ofBixa orellana presented cytotoxicity at concentrations below100 120583gmL [81]
8 Toxicological Activities
Currently concerns about the effect of synthetic dyes onhuman health are incontestable making people increasinglychoose those of natural origin believing that they are devoidof toxic effects This is not entirely true because even amedication from a natural source can be a poison depending
6 The Scientific World Journal
Table3Biologicalactiv
ities
ofextractsof
annatto
inAmerican
coun
tries
Cou
ntry
biologicalactiv
ityPartused
Type
ofextract
Organism
teste
dMod
elteste
dDoseu
sed
Activ
ityRe
ferences
Argentin
aAntibacteria
lLE
EtOH
Bacillussubtilis
Invitro
5mgmL
Inactiv
e[70]
Escherich
iacoli
Invitro
5mgmL
Inactiv
e[70]
Micrococcusluteus
Invitro
5mgmL
Inactiv
e[70]
Pseudomonas
aeruginosa
Invitro
5mgmL
Inactiv
e[70]
Staphylococcus
aureus
Invitro
5mgmL
Inactiv
e[70]
Antifu
ngal
LEEtOH
Aspergillus
niger
Invitro
5mgmL
Inactiv
e[70]
Cand
idaalbicans
Invitro
5mgmL
Inactiv
e[70]
Antivira
lSE
EtOH
VirusH
erpessim
plex
1Cell
cultu
re078
mgmL
Inactiv
e[71]
Insecticidal
AP
MeO
HInsect
Sitophilu
soryzae
5Inactiv
e[71]
Brazil
Antim
alarial
SECH
Cl3
Mou
sePlasmodium
berghei
100m
gkg
Inactiv
e[26]
Antioxidant
SEEtOH
Invitro
DPP
Hassay
01g
Lminus1
Activ
e[6]
Insectrepellent
SEPetr
eth
Ham
ster
Lutzom
yialongipalpis
1gL
Activ
e[72]
SEEtOH
Mosqu
itoAe
desa
egypti
182mgmL
Activ
e[6]
Molluscicidal
SEEtOH
Con
chBiom
phalariagla
brata
10000
ppm
Inactiv
e[73]
Mutagenic
Powder
Mou
seBo
nemarrowcells
10670
ppm
Inactiv
e[67]
Toxicity
SEPo
wder
Rat
Invivo
500m
gkg
Inactiv
e[74]
Antileish
manial
LERO
EtOH
Leish
maniaam
azonensis
Invitro
012ndash25mgmL
Activ
e[75]
Antileish
manial
SEOE
Leish
maniaam
azonensis
Invitro
10501005001000120583gmL
Activ
e[76]
Hyperlip
idem
iaSE
H2O
Mou
seIn
vitro
400and800m
gkg
Activ
e[77]
Colom
bia
Snakebite
LEEtOH
Mou
seBo
throps
atrox
LD50gt260120583
ganim
alAc
tive
[29]
CostaRica
Anti-infl
ammatory
ROEtOH
Rat
Pawedem
acarrageenan
100m
gkg
Inactiv
e[78]
Cuba Positiveino
tropice
ffect
AP
H2O
Guineap
igIsolated
atriu
m320120583
LInactiv
e[79]
Antim
alarial
SEPlasmodium
gallina
ceum
falciparum
Invivoin
vitro
500m
gkg
Activ
e[80]
Cytotoxic
SEEtOH
Tumor
cells
Invitro
39ndash
250m
gmL
Activ
e[81]
Ecuado
rAntifu
ngal
LEMeO
HAspergillus
niger
Invitro
10mgdisk
Inactiv
e[82]
Cand
idaalbicans
Invitro
10mgdisk
Inactiv
e[82]
Cryptococcus
neoforman
sIn
vitro
10mgdisk
Inactiv
e[82]
Fusariu
moxysporum
Invitro
10mgdisk
Inactiv
e[82]
Neurospora
crassa
Invitro
10mgdisk
Inactiv
e[82]
Penicilliu
mpurpurogenum
Invitro
10mgdisk
Inactiv
e[82]
Trich
ophytonmentagrophytes
Invitro
10mgdisk
Activ
e[82]
The Scientific World Journal 7
Table3Con
tinued
Cou
ntry
biologicalactiv
ityPartused
Type
ofextract
Organism
teste
dMod
elteste
dDoseu
sed
Activ
ityRe
ferences
Guatemala
Antibacteria
lLE
Vario
usEscherich
iacoli
Invitro
50120583Ldisk
Inactiv
e[83]
Pseudomonas
aeruginosa
Invitro
MICgt10mgmL
Inactiv
e[83]
Salm
onellatyphi
Invitro
MICgt10mgmL
Inactiv
e[83]
Shigelladysenteriae
Invitro
50120583L
Inactiv
e[83]
Staphylococcus
aureus
Invitro
MICgt10mgmL
Inactiv
e[83]
Antifu
ngal
LEH
2OAspergillus
flavus
Invitro
MICgt10mgmL
Inactiv
e[84]
Cand
idaalbicans
Invitro
MICgt10mgmL
Inactiv
e[84]
Microsporum
gypseum
Invitro
MICgt10mgmL
Inactiv
e[84]
Antigon
orrheal
LEEtOH
Neisseriagonorrhea
Invitro
50120583Ldisk
Activ
e[32]
Antitrypanosom
alLE
EtOH
Trypanosom
acruzi
Invitro
MICgt1m
gmL
Inactiv
e[83]
Cytotoxic
LEH
2OCr
ustacean
Artemiasalin
aLC
50gt10
00pp
mInactiv
e[83]
Inhibof
plateletaggregation
SE
Invitro
Thrombinaggregation
IC50
0795m
gmL
Inactiv
e[35]
Haw
aii
Con
traceptiv
eRO
Mou
se
02m
Lanim
alInactiv
e[85]
Jamaica
Hypoglycemic
SECH
Cl3
Dog
1gAc
tive
[39]
H2O
Dog
200m
Lanim
alAc
tive
[39]
Antioxidant
SEEtOH
Invitro
Invitro
025
and25120583
gmL
Activ
e[86]
Mexico
Allergenic
SEOil
Hum
an25120583L
person
Activ
e[87]
Paragu
ayInsecticidal
SEPetr
ether
Insect
Rhodnius
negle
ctus
50120583g
Inactiv
e[42]
Puerto
Rico
Molluscicidal
TPH
2OCon
chLymna
eacubensis
LD100gt1M
ppm
Inactiv
e[88]
Dom
inican
Repu
blic
Cytotoxic
SEEtOH
Cellculture
Molt4
cells
200120583
gmL
Inactiv
e[89]
Trinidad
andTo
bago
Antibacteria
lSE
EtOAc
Escherich
iacoli
Invitro
1000120583gmL
Inactiv
e[90]
Pseudomonas
aeruginosa
Invitro
1000120583gmL
Inactiv
e[90]
USA A
nticon
vulsa
ntRA
EtOH
Mou
seSeizureselectroshock
100m
gkg
Inactiv
e[91]
Rat
Seizurespentylenetetrazole
400m
gkg
Inactiv
e[91]
Antim
alarial
SECH
Cl3
Chicken
Plasmodium
gallina
ceum
388m
gkg
Inactiv
e[92]
Mutagenic
SEMeO
HSalm
onellatyphim
urium
100m
gplaque
Inactiv
e[93]
H2O
Invitro
Placentaltroph
oblasts
100m
gplaque
Inactiv
e[93]
Hypotensiv
eRA
EtOH
Rat
50mgkg
Activ
e[93]
Toxicity
RAH
2OMou
seLD
50gt700m
gkg
Inactiv
e[92]
LEleafAP
aeria
lpartTP
totalplantRO
roo
tSE
seedno
tgivenLD5050
lethaldo
seIC5
0concentrationthatinhibits50of
thee
ffectM
ICm
inim
uminhibitory
concentration
8 The Scientific World Journal
on the dose that is administered The failure to require in-depth data related to toxicological and chemical analysesfor the registration of food additives derived from naturalsources [67 74] certainly makes the information aboutpossible unwanted effects andor pharmacological activitiesresulting from their use much rarer than expected in view ofthe importance of the topic In Brazil the use of annatto is sowidespread that its safety is not even questioned
Paumgartten et al [91] evaluated the toxicity of annattoextracts in rats Doses up to 500mgkg body weightdaywere introduced directly into the stomach of pregnant ratsto evaluate the effect on the mother and fetus and noadverse effects were found for either The annatto extract didnot induce an increase in the incidence of visible externalvisceral or skeletal anomalies in the fetuses Therefore thestudy suggested that the annatto extract was not toxic to ratsnor was it embryotoxic Studies performed in Brazil by Alvesde Lima et al [67] where extracts of annatto weremixed withthe food of male rats showed that the concentrations testedhad no mutagenic or antimutagenic activity in their bonemarrow cells A parallel toxicity study conducted byHagiwaraet al [74] showed that 01 annatto extract administered forthirteen weeks in the feed of male and female rats did notshow any adverse effects However when higher doses wereadministered (03 and 09) the authors noticed an increasein liver weight as well as changes in blood chemistriesincluding increase in alkaline phosphatase phospholipidsand total protein as well as albumin and albuminglobulinratio
Hagiwara et al [74] also evaluated extracts of annattofor liver carcinogenicity in rats and found no evidence ofliver tumors even when given to animals at a high dose of200mgkg body weightday compared to an acceptable doseof 00 to 0065mgkgday thus indicating that the dangerof a hepatocarcinogenic effect in humans may be absent ornegligible
A toxicity test was performedwith extracts obtained fromboth plant seeds and shoots and no significant effect wasobserved The experiments were performed in the UnitedStates using mice as the animal model and it was found thatthe LD50 was greater than 700mgkg [92]
9 Correlation between the BiologicalActivities Phytochemistry and theTraditional Uses of Bixa orellana
Table 1 shows that many of the traditional uses of Bixaorellana are the same in several countries of South andCentral America which suggests its effectiveness as a ther-apeutic agent Extracts of Bixa orellana showed biologicalactivities such as antioxidant hypotensive molluscicideand antimalarial against A549 cells for carcinoma of thelung allergy hypoglycemic antifungal antioxidant insectrepellent antigonococcal and antivenom serum and some ofthem are in accordance with the traditional use for examplein Brazil it is used to extract the seeds with purpose repellentinsecticide and antimalaria and scientific studies in the samecountrywith the Lutzomyia longipalpis insect repellent action
and prove a study in Cuba proved the pharmacological actionfor antimalarial activity when tested against Plasmodiumberghei Some of them are in accordance with the traditionaluse for example seed extracts have been used in Brazil andCuba as insect repellent and antimalarial Antioxidant andinsect repellent activities can be attributed to the carotenoidsand the essential and fixed oils respectively
Despite the previous reports about the presence of com-ponents with anti-inflammatory properties such as salicylicacid lutein polyphenols and tannins this activity has not yetbeen proven for Bixa orellana extracts Similarly the plantrsquosessential and fixed oils have shown antibacterial propertiesalthough this activity has not been proven too
In general the data obtained in this review do not allowcorrelations between the biologic activities tested in vitro or invivo with the compounds identified in this species Howevertaking into account the related activities such as the antipara-sitic effect and the lack of mutagenic and cytotoxicity activityit is possible to consider Bixa orellana as a potential source forthe development of phytopharmaceutical products
In conclusion the studies discussed in this review repre-sent a rich database around the Bixa orellana activities andits potential uses which evokes the feasibility of phytophar-maceuticals to treat some diseases whenever an antioxidanthypotensor or hypoglycemiant activity is necessary
Although the commercial exploitation of this species iswell established there are very few studies on its pharma-cological effects Considering the need for developing a safeand effective product more studies should be performed inorder to confirm other biological activities supported by thepopular uses of Bixa orellana
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors are grateful to CNPqPRONEXFAPESQ andCAPES for financial support and to the NAPRALERTDatabase of the University of Illinois USA for the literatureon Bixa orellana A Leyva helped in editing the Englishlanguage of the paper
References
[1] M B Perecin O A Bovi and N B Maia ldquoPesquisa complantas aromaticas medicinais corantes o papel do InstitutoAgronomicordquo O Agronomico vol 54 pp 21ndash24 2002
[2] M E A Elias G Schroth J L V Macedo M S S Motaand S A DrsquoAngelo ldquoMineral nutrition growth and yields ofannatto trees (Bixa orellana) in agroforestry on an AmazonianFerralsolrdquo Experimental Agriculture vol 38 no 3 pp 277ndash2892002
[3] A R R Bastos J G Carvalho R P Assis and A B C FilholdquoMarcha de absorcao de nutrientes em urucum ( Bixa orellanaL) tipo cultivado piave vermelha em fase de viveirordquoCerne vol5 pp 76ndash85 1999
The Scientific World Journal 9
[4] E PThomasM Colvin S B Rosen C Zuccarini and S PetzerldquoHIV prevalence study and costing analysis undertaken for thedevelopment of an HIVAIDS workplace strategy for buffalocity municipalityrdquo Tech Rep Medical Research Council Buf-falo NY USA 2005
[5] C F Franco ldquoO Agronegocio do urucum na regiao Nordesterdquo 1Reuniao Nacional da Cadeia Produtiva de Urucum CD-Rom2007
[6] A Giorgi P De Marinis G Granelli L M Chiesa and SPanseri ldquoSecondary metabolite profile antioxidant capacityand mosquito repellent activity of Bixa orellana from BrazilianAmazon regionrdquo Journal of Chemistry vol 2013 Article ID409826 10 pages 2013
[7] J S Silva M D Moura R A G Oliveira M F F Dinizand J M Barbosa-Filho ldquoNatural product inhibitors of ovarianneoplasiardquo Phytomedicine vol 10 no 2-3 pp 221ndash232 2003
[8] F C F Sousa C T V Melo C O M Cito et al ldquoPlantasmedicinais e seus constituintes bioativos uma revisao dabioatividade e potenciais benefıcios nos disturbios da ansiedadeem modelos animaisrdquo Revista Brasileira de Farmacognosia vol18 pp 642ndash654 2008
[9] L J Quintans Jr J R G S Almeida J T Lima et al ldquoPlantswith anticonvulsant propertiesmdasha reviewrdquo Revista Brasileira deFarmacognosia vol 18 pp 798ndash819 2008
[10] HD S Falcao J A Leite JM Barbosa-Filho et al ldquoGastric andduodenal antiulcer activity of alkaloids a reviewrdquoMolecules vol13 no 12 pp 3198ndash3223 2008
[11] H S Falcao I R Mariath M F F M Diniz L M Batista andJ M Barbosa-Filho ldquoPlants of the American continent withantiulcer activityrdquo Phytomedicine vol 15 no 1-2 pp 132ndash1462008
[12] I R Mariath H D S Falcao J M Barbosa-Filho et al ldquoPlantsof the American continent with antimalarial activityrdquo RevistaBrasileira de Farmacognosia vol 19 no 1 pp 158ndash192 2009
[13] J E R Hon P M Soares C L Melo et al ldquoAtividadefarmacologica da monocrotalina isolada de plantas do generoCrotalariardquo Revista Brasileira de Farmacognosia vol 20 pp453ndash458 2010
[14] R N Almeida D S Navarro and J M Barbosa-Filho ldquoPlantswith central analgesic activityrdquo Phytomedicine vol 8 no 4 pp310ndash322 2001
[15] N Z T Jesus H S Falcao I F Gomes et al ldquoTanninspeptic ulcers and related mechanismsrdquo International Journal ofMolecular Sciences vol 13 no 3 pp 3203ndash3228 2012
[16] L G Rocha J R G S Almeida R O Macedo and J MBarbosa-Filho ldquoA review of natural products with antileishma-nial activityrdquo Phytomedicine vol 12 no 6-7 pp 514ndash535 2005
[17] G R M Lima C A Montenegro C L F Almeida PF Athayde-Filho J M Barbosa-Filho and L M BatistaldquoDatabase survey of anti-inflammatory plants in South Amer-ica a reviewrdquo International Journal ofMolecular Sciences vol 12no 4 pp 2692ndash2749 2011
[18] K S De Lira Mota G E N Dias M E F Pinto et alldquoFlavonoids with gastroprotective activityrdquo Molecules vol 14no 3 pp 979ndash1012 2009
[19] A L Souto J F Tavares M S da Silva M F F M de Diniz P Fde Athayde-Filho and J M Barbosa Filho ldquoAnti-inflammatoryactivity of alkaloids an update from 2000 to 2010rdquo Moleculesvol 16 no 10 pp 8515ndash8534 2011
[20] F L Silva D C H Fischer J F Tavares M S Silva P Fde Athayde-Filho and J M Barbosa-Filho ldquoCompilation of
secondary metabolites from Bidens pilosa LrdquoMolecules vol 16no 2 pp 1070ndash1102 2011
[21] J R Filho H de Sousa Falcao L M Batista J M B Filho andM R Piuvezam ldquoEffects of plant extracts on HIV-1 proteaserdquoCurrent HIV Research vol 8 no 7 pp 531ndash544 2010
[22] JM Barbosa-Filho A A Alencar X P Nunes et al ldquoSources ofalpha- beta- gamma- delta- and epsilon-carotenes a twentiethcentury reviewrdquo Revista Brasileirta de Farmacogn vol 18 no 1pp 135ndash154 2008
[23] S N S Silva C L F Amaral and T N H Reboucas ldquoAdoptionof conservation practices on farm and selection of varieties byproducers of annatto in the city of Vitoria da Conquista-BArdquoRevista Brasileira de Agroecologica vol 5 pp 106ndash113 2010
[24] A L Bandoni M E Mendiondo R V D Rondina and J DCoussio ldquoSurvey of Argentine medicinal plants I Folklore andphytochemical screeningrdquo Lloydia vol 35 no 1ndash4 pp 69ndash801972
[25] G H Garcia R Campos R A de Torres et al ldquoAntiherpeticactivity of some Argentine medicinal plantsrdquo Fitoterapia vol61 no 6 pp 542ndash546 1990
[26] M G L Brandao T S M Grandi E M M Rocha D RSawyer and A U Krettli ldquoSurvey of medicinal plants used asantimalarials in the Amazonrdquo Journal of Ethnopharmacologyvol 36 no 2 pp 175ndash182 1992
[27] M P Correa Dicionario das Plantas Uteis do Brasil e dasExoticas Cultivadas vol 4 Ministerio da AgriculturaIBDF Riode Janeiro Brasil 1978
[28] G S Hirschmann and A R de Arias ldquoA survey of medicinalplants of minas gerais Brazilrdquo Journal of Ethnopharmacologyvol 29 no 2 pp 159ndash172 1990
[29] R Otero R Fonnegra S L Jimenez et al ldquoSnakebites andethnobotany in the northwest region of Colombia Part Itraditional use of plantsrdquo Journal of Ethnopharmacology vol 71no 3 pp 493ndash504 2000
[30] H Garcia-Barriga Flora Medicinal de Colombia vol 2 Univer-sidad Nacional Bogota Colombia 1975
[31] J T Roig y Mesa Plantas Medicinales Aromaticas o Venenosasde Cuba Ministerio de Agricultura Havana Cuba 1945
[32] A Caceres H Menendez E Mendez et al ldquoAntigonorrhoealactivity of plants used inGuatemala for the treatment of sexuallytransmitted diseasesrdquo Journal of Ethnopharmacology vol 48no 2 pp 85ndash88 1995
[33] J A Duke and R V Martinez Amazonian EthnobotanicalDictionary CRC Press Boca Raton Fla USA 1994
[34] V R Ramirez L J Mostacero A E Garcia et al VegetalesEmpleados enMedicina Tradicional Norperuana Banco Agrariodel Peru Universidad Nacional de Trujillo Trujillo Peru 1988
[35] R Villar J M Calleja C Morales and A Caceres ldquoScreeningof 17 Guatemalan medicinal plants for platelet antiaggregantactivityrdquo Phytotherapy Research vol 11 pp 441ndash445 1997
[36] L M Giron V Freire A Alonzo and A Caceres ldquoEthnob-otanical survey of the medicinal flora used by the Caribs ofGuatemalardquo Journal of Ethnopharmacology vol 34 no 2-3 pp173ndash187 1991
[37] D L Lentz ldquoMedicinal and other economic plants of the PayaofHondurasrdquo Economic Botany vol 47 no 4 pp 358ndash370 1993
[38] D L Lentz A M Clark C D Hufford et al ldquoAntimi-crobial properties of Honduran medicinal plantsrdquo Journal ofEthnopharmacology vol 63 no 3 pp 253ndash263 1998
[39] E Y Morrison and M E West ldquoThe effect of Bixa orellana(Annatto) on blood sugar levels in the anaesthetized dogrdquoWestIndian Medical Journal vol 34 no 1 pp 38ndash42 1985
10 The Scientific World Journal
[40] F G Coe and G J Anderson ldquoScreening of medicinal plantsused by the Garıfuna of eastern Nicaragua for bioactive com-poundsrdquo Journal of Ethnopharmacology vol 53 no 1 pp 29ndash501996
[41] B Barrett ldquoMedicinal plants of Nicaraguarsquos Atlantic CoastrdquoEconomic Botany vol 48 no 1 pp 8ndash20 1994
[42] G Schmeda-Hirschmann and A R de Arias ldquoA screeningmethod for natural products on triatomine bugsrdquo PhytotherapyResearch vol 6 no 2 pp 68ndash73 1992
[43] G E Simpson ldquoFolk medicine in Trinidadrdquo The Journal ofAmerican Folklore vol 75 no 298 pp 326ndash340 1962
[44] D Mahabir and M C Gulliford ldquoUse of medicinal plants fordiabetes in Trinidad and Tobagordquo Revista Panamericana deSalud Publica vol 1 no 3 pp 174ndash179 1997
[45] E S Ayensu ldquoMedicinal plants of theWest IndiesrdquoUnpublishedManuscript 1978
[46] A Z Mercadante A Steck D Rodriguez-Amaya H Pfanderand G Britton ldquoIsolation of methyl 91015840Z-APO-61015840-lycopenoatefrom Bixa Orellanardquo Phytochemistry vol 41 no 4 pp 1201ndash1203 1996
[47] E Angelucci H K Arima E A Kumagai and I AnnattoldquoPreliminary data of the chemical compositionrdquo Coletanea doInstituto de Tecnologia de Alimentos vol 11 pp 89ndash96 1980
[48] A S L Tirimanna ldquoStudy of the carotenoid pigments of Bixaorellana L Seeds by thin layer chromatographyrdquo MikrochimicaActa vol 76 no 1-2 pp 11ndash16 1981
[49] J M Barbosa-Filho R N Silva-Filho B F Lira et al ldquoTeor debixina em quatro variedades de Bixa orellana L cultivadas naParaıbardquo Revista Brasileira de Farmacognosia vol 7-8 pp 41ndash47 1998
[50] A Z Mercadante A Steck and H Pfander ldquoIsolation andstructure elucidation of minor carotenoids from annatto (Bixaorellana L) seedsrdquo Phytochemistry vol 46 no 8 pp 1379ndash13831997
[51] C Prentice-Hernandez and O Rusig ldquoAnnatto (Bixa orellanaL) extract obtained using ethyl alcohol as a solventrdquo Arquivosde Biologia e Tecnologia vol 35 pp 63ndash74 1992
[52] A Z Mercadante ldquoComposition of carotenoids from annattordquoACS Symposium Series vol 775 pp 92ndash101 2001
[53] M J Scotter L A Wilson G P Appleton and L CastleldquoAnalysis of Annatto (Bixa orellana) Food Coloring Formula-tions 1 Determination of Coloring Components and ColoredThermal Degradation Products by High-Performance LiquidChromatography with Photodiode Array Detectionrdquo Journal ofAgricultural and Food Chemistry vol 46 no 3 pp 1031ndash10381998
[54] A J Degnan J H von Elbe and R W Hartel ldquoExtraction ofannatto seed pigment by supercritical carbon dioxiderdquo Journalof Food Science vol 56 pp 1655ndash1659 1991
[55] A ZMercadante A Steck andH Pfander ldquoIsolation and iden-tification of new apocarotenoids from annatto (Bixa orellana)seedsrdquo Journal of Agricultural and Food Chemistry vol 45 no4 pp 1050ndash1054 1997
[56] S G Anderson M G Nair A Chandra and E MorrisonldquoSupercritical fluid carbon dioxide extraction of annatto seedsand quantification of trans-bixin by high pressure liquid chro-matographyrdquo Phytochemical Analysis vol 8 pp 247ndash249 1997
[57] J M Barbosa-Filho Bixa orellana Retrospectiva de usos pop-ulares atividades biologicas fitoquımica e emprego na fito-cosmetica no continente americano Simposio Brasileiro doUrucummdashSIMBRAU Joao Pessoa Brazil 2006
[58] J Revilla Plantas da Amazonia Oportunidades Economicas eSustentaveis Manaus Programa de Desenvolvimento Empre-sarial e Tecnologico 2nd edition 2001
[59] F Oliveira G Akisue and M K Akisue FarmacognosiaAtheneu Sao Paulo Brazil 1996
[60] J Alonso Tratado de Fitofarmacos y Nutraceuticos CorpusRosario Argentina 2004
[61] C O Franco E G Fabri M Barreiro Neto M H Manfiolli MN C Harder and N C Rucker Urucum Sistema de Producaopara o Brasil Emepa-Pb Apta Joao Pessoa Brazil 2008
[62] P A Venugopalan G A Giridhar and A G RavishankarldquoFood Ethanobotanical and diversified applications of Bixaorellana L a scope for its improvement through biotechnolog-ical mediationrdquo Indian Journal of Fundamental and Applied LifeSciences vol 1 pp 9ndash31 2011
[63] L Taylor Herbal Secrets of the Rainforest Sage Press RocklinCalif USA 2nd edition 2002
[64] J S Oliveira Caracterizacao Extracao e Purificacao por Cro-matografia de Compostos de Urucum (Bixa orellana L) [tesisdoctoral en Ingenierıa Quımic] Universidade Federal de SantaCatarina Florianopolis Brazil 2005
[65] A Z Mercadante A Steck and H Pfander ldquoThree minorcarotenoids from annatto (Bixa orellana) seedsrdquo Phytochem-istry vol 52 no 1 pp 135ndash139 1999
[66] V Galindo-Cuspinera M B Lubran and S A Rankin ldquoCom-parison of volatile compounds in water- and oil-soluble annatto(Bixa orellana L) extractsrdquo Journal of Agricultural and FoodChemistry vol 50 no 7 pp 2010ndash2015 2002
[67] R O Alves de Lima L Azevedo L R Ribeiro and D M FSalvadori ldquoStudy on the mutagenicity and antimutagenicity ofa natural food colour (annatto) in mouse bone marrow cellsrdquoFood and Chemical Toxicology vol 41 no 2 pp 189ndash192 2003
[68] L R P Lima T T Oliveira T J Nagem et al ldquoBixina norbixinae quercetina e seus efeitos no metabolismo lipıdico de coelhosrdquoBrazilian Journal of Veterinary Research andAnimal Science vol38 pp 196ndash200 2001
[69] J D Fontana S V Mendes D S Persike L F Peracetta andM Passos ldquoCarotenoides cores atraentes e acao biologicardquoBiotecnologia Ciencia amp Desenvolvimento vol 2 p 13 2000
[70] C A Penna M Radice G O Gutkind et al ldquoAntibacterial andantifungal activities of some Argentinean plantsrdquo Fitoterapiavol 65 no 2 pp 172ndash174 1994
[71] A M Broussalis G E Ferraro V S Martino R Pinzon J DCoussio and J C Alvarez ldquoArgentine plants as potential sourceof insecticidal compoundsrdquo Journal of Ethnopharmacology vol67 no 2 pp 219ndash223 1999
[72] A Rojas de Arias G Schmeda-Hirschmann and A FalcaoldquoFeeding deterrency and insecticidal effects of plant extracts onLutzomyia longipalpisrdquo Phytotherapy Research vol 6 no 2 pp64ndash67 1992
[73] M S Pinheiro and M Z Rouquayrol ldquoMolluscicidal activityof plants from Northeast Brazilrdquo Revista Brasileira de PesquisasMedicas e Biologicas vol 7 pp 389ndash394 1974
[74] A Hagiwara N Imai T Ichihara et al ldquoA thirteen-week oraltoxicity study of annatto extract (norbixin) a natural food colorextracted from the seed coat of annatto (Bixa orellana L) inSprague-Dawley ratsrdquoFood andChemical Toxicology vol 41 no8 pp 1157ndash1164 2003
[75] C R Almeida R B Silva M J Marques and J K ChavascoldquoEvaluation of antiparasitic activity of hydroethanolic extractsfrom root stem and leaf of Bixa orellana L on Leishmania
The Scientific World Journal 11
amazonensis samplesrdquo Revista da Universidade Vale do RioVerde vol 10 no 2 pp 384ndash391 2012
[76] M V Lopes V C Desoti A D O Caleare T Ueda-NakamuraS O Silva and C V Nakamura ldquoMitochondria superoxideanion production contributes to geranylgeraniol-induced deathin leishmania amazonensisrdquo Evidence-Based Complementaryand Alternative Medicine vol 2012 Article ID 298320 9 pages2012
[77] J M Ferreira D F Sousa M B Dantas et al ldquoEffects of BixaorellanaL seeds onhyperlipidemiardquoPhytotherapyResearch vol27 no 1 pp 144ndash147 2013
[78] P S BenoitHH S FongGH Svoboda andN R FarnsworthldquoBiological and phytochemical evaluation of plants XIV Anti-inflammatory evaluation of 163 species of plantsrdquo Lloydia vol39 no 2-3 pp 160ndash171 1976
[79] D Carabajal A Casaco L Arruzazabala R Gonzalez andV Fuentes ldquoPharmacological screening of plant decoctionscommonly used in Cuban folk medicinerdquo Journal of Ethnophar-macology vol 33 no 1-2 pp 21ndash24 1991
[80] A F C Valdes J M Martınez D A Rodrıguez R S Lizamaand Y G Gaiten ldquoActividad antimalarica de un extractohidroalcoholico de Bixa orellanaLrdquo Revista Cubana de Medic-ina Tropical vol 63 pp 181ndash185 2011
[81] A D Garcıa H R Sanchez and R S Lizama ldquoCitotoxicidadde extractos de plantas medicinales sobre la lınea celularde carcinoma de pulmon humano A549rdquo Revista Cubana deFarmacia vol 45 pp 101ndash108 2011
[82] B Freixa R Vila L Vargas N Lozano T Adzet and SCanigueral ldquoScreening for antifungal activity of nineteen LatinAmerican plantsrdquo Phytotherapy Research vol 12 no 6 pp 427ndash430 1998
[83] A Caceres B Lopez S Gonzalez I Berger I Tada and JMaki ldquoPlants used in Guatemala for the treatment of pro-tozoal infections I Screening of activity to bacteria fungiand American trypanosomes of 13 native plantsrdquo Journal ofEthnopharmacology vol 62 no 3 pp 195ndash202 1998
[84] A Caceres O Cano B Samayoa and L Aguilar ldquoPlants usedin Guatemala for the treatment of gastrointestinal disorders1 Screening of 84 plants against enterobacteriardquo Journal ofEthnopharmacology vol 30 no 1 pp 55ndash73 1990
[85] A S Matsui S Hoskin M Kashiwagi et al ldquoA survey ofnatural products from Hawaii and other areas of the Pacificfor an antifertility effect in micerdquo Internationale Zeitschrift furKlinische PharmakologieTherapie und Toxikologie vol 5 no 1pp 65ndash69 1971
[86] M Abayomi A S Adebayo D Bennett R Porter and JS Campbell ldquoIn vitro antioxidant activity of Bixa orellana(Annatto) seed extractrdquo Journal of Applied PharmaceuticalScience vol 4 no 2 pp 101ndash106 2014
[87] NW Dunham and K R Allard ldquoA preliminary pharmacologicinvestigation of the roots of Bixa orellanardquo Journal of theAmerican Pharmacist Associantion vol 49 pp 218ndash219 1960
[88] F RMedina andRWoodbury ldquoTerrestrial plantsmolluscicidalto lymnaeid hosts of Fasciliasis hepatica in Puerto Ricordquo Journalof Agricultura of the University of Puerto Rico vol 63 pp 366ndash376 1979
[89] B Weniger Y Jiang A Oulad-Ali L Italiano J P Beck and RAnton ldquoBiological effects of bixin and Bixa orellana extracts onlymphoid cells in culturerdquo Planta Medica vol 59 no 7 articleA680 1993
[90] CM Chariandy C E Seaforth R H Phelps G V Pollard andB P S Khambay ldquoScreening of medicinal plants from Trinidad
and Tobago for antimicrobial and insecticidal propertiesrdquoJournal of Ethnopharmacology vol 64 no 3 pp 265ndash270 1999
[91] F J R Paumgartten R R Carvalho I B Araujo et alldquoEvaluation of the developmental toxicity of annatto in the ratrdquoFood and Chemical Toxicology vol 40 no 11 pp 1595ndash16012002
[92] C F Spencer F R Koniuszy E F Rogers et al ldquoSurvey of plantsfor antimalarial activityrdquo Lloydia vol 10 no 3 pp 145ndash174 1947
[93] H Mikkelsen J C Larsen and F Tarding ldquoHypersensitivityreactions to food colours with special reference to the naturalcolour annatto extract (butter colour)rdquo Toxicological Aspects ofFood Safety vol 1 pp 141ndash143 1978
Submit your manuscripts athttpwwwhindawicom
PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom
Volume 2014
ToxinsJournal of
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Pharmaceutics
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
6 The Scientific World Journal
Table3Biologicalactiv
ities
ofextractsof
annatto
inAmerican
coun
tries
Cou
ntry
biologicalactiv
ityPartused
Type
ofextract
Organism
teste
dMod
elteste
dDoseu
sed
Activ
ityRe
ferences
Argentin
aAntibacteria
lLE
EtOH
Bacillussubtilis
Invitro
5mgmL
Inactiv
e[70]
Escherich
iacoli
Invitro
5mgmL
Inactiv
e[70]
Micrococcusluteus
Invitro
5mgmL
Inactiv
e[70]
Pseudomonas
aeruginosa
Invitro
5mgmL
Inactiv
e[70]
Staphylococcus
aureus
Invitro
5mgmL
Inactiv
e[70]
Antifu
ngal
LEEtOH
Aspergillus
niger
Invitro
5mgmL
Inactiv
e[70]
Cand
idaalbicans
Invitro
5mgmL
Inactiv
e[70]
Antivira
lSE
EtOH
VirusH
erpessim
plex
1Cell
cultu
re078
mgmL
Inactiv
e[71]
Insecticidal
AP
MeO
HInsect
Sitophilu
soryzae
5Inactiv
e[71]
Brazil
Antim
alarial
SECH
Cl3
Mou
sePlasmodium
berghei
100m
gkg
Inactiv
e[26]
Antioxidant
SEEtOH
Invitro
DPP
Hassay
01g
Lminus1
Activ
e[6]
Insectrepellent
SEPetr
eth
Ham
ster
Lutzom
yialongipalpis
1gL
Activ
e[72]
SEEtOH
Mosqu
itoAe
desa
egypti
182mgmL
Activ
e[6]
Molluscicidal
SEEtOH
Con
chBiom
phalariagla
brata
10000
ppm
Inactiv
e[73]
Mutagenic
Powder
Mou
seBo
nemarrowcells
10670
ppm
Inactiv
e[67]
Toxicity
SEPo
wder
Rat
Invivo
500m
gkg
Inactiv
e[74]
Antileish
manial
LERO
EtOH
Leish
maniaam
azonensis
Invitro
012ndash25mgmL
Activ
e[75]
Antileish
manial
SEOE
Leish
maniaam
azonensis
Invitro
10501005001000120583gmL
Activ
e[76]
Hyperlip
idem
iaSE
H2O
Mou
seIn
vitro
400and800m
gkg
Activ
e[77]
Colom
bia
Snakebite
LEEtOH
Mou
seBo
throps
atrox
LD50gt260120583
ganim
alAc
tive
[29]
CostaRica
Anti-infl
ammatory
ROEtOH
Rat
Pawedem
acarrageenan
100m
gkg
Inactiv
e[78]
Cuba Positiveino
tropice
ffect
AP
H2O
Guineap
igIsolated
atriu
m320120583
LInactiv
e[79]
Antim
alarial
SEPlasmodium
gallina
ceum
falciparum
Invivoin
vitro
500m
gkg
Activ
e[80]
Cytotoxic
SEEtOH
Tumor
cells
Invitro
39ndash
250m
gmL
Activ
e[81]
Ecuado
rAntifu
ngal
LEMeO
HAspergillus
niger
Invitro
10mgdisk
Inactiv
e[82]
Cand
idaalbicans
Invitro
10mgdisk
Inactiv
e[82]
Cryptococcus
neoforman
sIn
vitro
10mgdisk
Inactiv
e[82]
Fusariu
moxysporum
Invitro
10mgdisk
Inactiv
e[82]
Neurospora
crassa
Invitro
10mgdisk
Inactiv
e[82]
Penicilliu
mpurpurogenum
Invitro
10mgdisk
Inactiv
e[82]
Trich
ophytonmentagrophytes
Invitro
10mgdisk
Activ
e[82]
The Scientific World Journal 7
Table3Con
tinued
Cou
ntry
biologicalactiv
ityPartused
Type
ofextract
Organism
teste
dMod
elteste
dDoseu
sed
Activ
ityRe
ferences
Guatemala
Antibacteria
lLE
Vario
usEscherich
iacoli
Invitro
50120583Ldisk
Inactiv
e[83]
Pseudomonas
aeruginosa
Invitro
MICgt10mgmL
Inactiv
e[83]
Salm
onellatyphi
Invitro
MICgt10mgmL
Inactiv
e[83]
Shigelladysenteriae
Invitro
50120583L
Inactiv
e[83]
Staphylococcus
aureus
Invitro
MICgt10mgmL
Inactiv
e[83]
Antifu
ngal
LEH
2OAspergillus
flavus
Invitro
MICgt10mgmL
Inactiv
e[84]
Cand
idaalbicans
Invitro
MICgt10mgmL
Inactiv
e[84]
Microsporum
gypseum
Invitro
MICgt10mgmL
Inactiv
e[84]
Antigon
orrheal
LEEtOH
Neisseriagonorrhea
Invitro
50120583Ldisk
Activ
e[32]
Antitrypanosom
alLE
EtOH
Trypanosom
acruzi
Invitro
MICgt1m
gmL
Inactiv
e[83]
Cytotoxic
LEH
2OCr
ustacean
Artemiasalin
aLC
50gt10
00pp
mInactiv
e[83]
Inhibof
plateletaggregation
SE
Invitro
Thrombinaggregation
IC50
0795m
gmL
Inactiv
e[35]
Haw
aii
Con
traceptiv
eRO
Mou
se
02m
Lanim
alInactiv
e[85]
Jamaica
Hypoglycemic
SECH
Cl3
Dog
1gAc
tive
[39]
H2O
Dog
200m
Lanim
alAc
tive
[39]
Antioxidant
SEEtOH
Invitro
Invitro
025
and25120583
gmL
Activ
e[86]
Mexico
Allergenic
SEOil
Hum
an25120583L
person
Activ
e[87]
Paragu
ayInsecticidal
SEPetr
ether
Insect
Rhodnius
negle
ctus
50120583g
Inactiv
e[42]
Puerto
Rico
Molluscicidal
TPH
2OCon
chLymna
eacubensis
LD100gt1M
ppm
Inactiv
e[88]
Dom
inican
Repu
blic
Cytotoxic
SEEtOH
Cellculture
Molt4
cells
200120583
gmL
Inactiv
e[89]
Trinidad
andTo
bago
Antibacteria
lSE
EtOAc
Escherich
iacoli
Invitro
1000120583gmL
Inactiv
e[90]
Pseudomonas
aeruginosa
Invitro
1000120583gmL
Inactiv
e[90]
USA A
nticon
vulsa
ntRA
EtOH
Mou
seSeizureselectroshock
100m
gkg
Inactiv
e[91]
Rat
Seizurespentylenetetrazole
400m
gkg
Inactiv
e[91]
Antim
alarial
SECH
Cl3
Chicken
Plasmodium
gallina
ceum
388m
gkg
Inactiv
e[92]
Mutagenic
SEMeO
HSalm
onellatyphim
urium
100m
gplaque
Inactiv
e[93]
H2O
Invitro
Placentaltroph
oblasts
100m
gplaque
Inactiv
e[93]
Hypotensiv
eRA
EtOH
Rat
50mgkg
Activ
e[93]
Toxicity
RAH
2OMou
seLD
50gt700m
gkg
Inactiv
e[92]
LEleafAP
aeria
lpartTP
totalplantRO
roo
tSE
seedno
tgivenLD5050
lethaldo
seIC5
0concentrationthatinhibits50of
thee
ffectM
ICm
inim
uminhibitory
concentration
8 The Scientific World Journal
on the dose that is administered The failure to require in-depth data related to toxicological and chemical analysesfor the registration of food additives derived from naturalsources [67 74] certainly makes the information aboutpossible unwanted effects andor pharmacological activitiesresulting from their use much rarer than expected in view ofthe importance of the topic In Brazil the use of annatto is sowidespread that its safety is not even questioned
Paumgartten et al [91] evaluated the toxicity of annattoextracts in rats Doses up to 500mgkg body weightdaywere introduced directly into the stomach of pregnant ratsto evaluate the effect on the mother and fetus and noadverse effects were found for either The annatto extract didnot induce an increase in the incidence of visible externalvisceral or skeletal anomalies in the fetuses Therefore thestudy suggested that the annatto extract was not toxic to ratsnor was it embryotoxic Studies performed in Brazil by Alvesde Lima et al [67] where extracts of annatto weremixed withthe food of male rats showed that the concentrations testedhad no mutagenic or antimutagenic activity in their bonemarrow cells A parallel toxicity study conducted byHagiwaraet al [74] showed that 01 annatto extract administered forthirteen weeks in the feed of male and female rats did notshow any adverse effects However when higher doses wereadministered (03 and 09) the authors noticed an increasein liver weight as well as changes in blood chemistriesincluding increase in alkaline phosphatase phospholipidsand total protein as well as albumin and albuminglobulinratio
Hagiwara et al [74] also evaluated extracts of annattofor liver carcinogenicity in rats and found no evidence ofliver tumors even when given to animals at a high dose of200mgkg body weightday compared to an acceptable doseof 00 to 0065mgkgday thus indicating that the dangerof a hepatocarcinogenic effect in humans may be absent ornegligible
A toxicity test was performedwith extracts obtained fromboth plant seeds and shoots and no significant effect wasobserved The experiments were performed in the UnitedStates using mice as the animal model and it was found thatthe LD50 was greater than 700mgkg [92]
9 Correlation between the BiologicalActivities Phytochemistry and theTraditional Uses of Bixa orellana
Table 1 shows that many of the traditional uses of Bixaorellana are the same in several countries of South andCentral America which suggests its effectiveness as a ther-apeutic agent Extracts of Bixa orellana showed biologicalactivities such as antioxidant hypotensive molluscicideand antimalarial against A549 cells for carcinoma of thelung allergy hypoglycemic antifungal antioxidant insectrepellent antigonococcal and antivenom serum and some ofthem are in accordance with the traditional use for examplein Brazil it is used to extract the seeds with purpose repellentinsecticide and antimalaria and scientific studies in the samecountrywith the Lutzomyia longipalpis insect repellent action
and prove a study in Cuba proved the pharmacological actionfor antimalarial activity when tested against Plasmodiumberghei Some of them are in accordance with the traditionaluse for example seed extracts have been used in Brazil andCuba as insect repellent and antimalarial Antioxidant andinsect repellent activities can be attributed to the carotenoidsand the essential and fixed oils respectively
Despite the previous reports about the presence of com-ponents with anti-inflammatory properties such as salicylicacid lutein polyphenols and tannins this activity has not yetbeen proven for Bixa orellana extracts Similarly the plantrsquosessential and fixed oils have shown antibacterial propertiesalthough this activity has not been proven too
In general the data obtained in this review do not allowcorrelations between the biologic activities tested in vitro or invivo with the compounds identified in this species Howevertaking into account the related activities such as the antipara-sitic effect and the lack of mutagenic and cytotoxicity activityit is possible to consider Bixa orellana as a potential source forthe development of phytopharmaceutical products
In conclusion the studies discussed in this review repre-sent a rich database around the Bixa orellana activities andits potential uses which evokes the feasibility of phytophar-maceuticals to treat some diseases whenever an antioxidanthypotensor or hypoglycemiant activity is necessary
Although the commercial exploitation of this species iswell established there are very few studies on its pharma-cological effects Considering the need for developing a safeand effective product more studies should be performed inorder to confirm other biological activities supported by thepopular uses of Bixa orellana
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors are grateful to CNPqPRONEXFAPESQ andCAPES for financial support and to the NAPRALERTDatabase of the University of Illinois USA for the literatureon Bixa orellana A Leyva helped in editing the Englishlanguage of the paper
References
[1] M B Perecin O A Bovi and N B Maia ldquoPesquisa complantas aromaticas medicinais corantes o papel do InstitutoAgronomicordquo O Agronomico vol 54 pp 21ndash24 2002
[2] M E A Elias G Schroth J L V Macedo M S S Motaand S A DrsquoAngelo ldquoMineral nutrition growth and yields ofannatto trees (Bixa orellana) in agroforestry on an AmazonianFerralsolrdquo Experimental Agriculture vol 38 no 3 pp 277ndash2892002
[3] A R R Bastos J G Carvalho R P Assis and A B C FilholdquoMarcha de absorcao de nutrientes em urucum ( Bixa orellanaL) tipo cultivado piave vermelha em fase de viveirordquoCerne vol5 pp 76ndash85 1999
The Scientific World Journal 9
[4] E PThomasM Colvin S B Rosen C Zuccarini and S PetzerldquoHIV prevalence study and costing analysis undertaken for thedevelopment of an HIVAIDS workplace strategy for buffalocity municipalityrdquo Tech Rep Medical Research Council Buf-falo NY USA 2005
[5] C F Franco ldquoO Agronegocio do urucum na regiao Nordesterdquo 1Reuniao Nacional da Cadeia Produtiva de Urucum CD-Rom2007
[6] A Giorgi P De Marinis G Granelli L M Chiesa and SPanseri ldquoSecondary metabolite profile antioxidant capacityand mosquito repellent activity of Bixa orellana from BrazilianAmazon regionrdquo Journal of Chemistry vol 2013 Article ID409826 10 pages 2013
[7] J S Silva M D Moura R A G Oliveira M F F Dinizand J M Barbosa-Filho ldquoNatural product inhibitors of ovarianneoplasiardquo Phytomedicine vol 10 no 2-3 pp 221ndash232 2003
[8] F C F Sousa C T V Melo C O M Cito et al ldquoPlantasmedicinais e seus constituintes bioativos uma revisao dabioatividade e potenciais benefıcios nos disturbios da ansiedadeem modelos animaisrdquo Revista Brasileira de Farmacognosia vol18 pp 642ndash654 2008
[9] L J Quintans Jr J R G S Almeida J T Lima et al ldquoPlantswith anticonvulsant propertiesmdasha reviewrdquo Revista Brasileira deFarmacognosia vol 18 pp 798ndash819 2008
[10] HD S Falcao J A Leite JM Barbosa-Filho et al ldquoGastric andduodenal antiulcer activity of alkaloids a reviewrdquoMolecules vol13 no 12 pp 3198ndash3223 2008
[11] H S Falcao I R Mariath M F F M Diniz L M Batista andJ M Barbosa-Filho ldquoPlants of the American continent withantiulcer activityrdquo Phytomedicine vol 15 no 1-2 pp 132ndash1462008
[12] I R Mariath H D S Falcao J M Barbosa-Filho et al ldquoPlantsof the American continent with antimalarial activityrdquo RevistaBrasileira de Farmacognosia vol 19 no 1 pp 158ndash192 2009
[13] J E R Hon P M Soares C L Melo et al ldquoAtividadefarmacologica da monocrotalina isolada de plantas do generoCrotalariardquo Revista Brasileira de Farmacognosia vol 20 pp453ndash458 2010
[14] R N Almeida D S Navarro and J M Barbosa-Filho ldquoPlantswith central analgesic activityrdquo Phytomedicine vol 8 no 4 pp310ndash322 2001
[15] N Z T Jesus H S Falcao I F Gomes et al ldquoTanninspeptic ulcers and related mechanismsrdquo International Journal ofMolecular Sciences vol 13 no 3 pp 3203ndash3228 2012
[16] L G Rocha J R G S Almeida R O Macedo and J MBarbosa-Filho ldquoA review of natural products with antileishma-nial activityrdquo Phytomedicine vol 12 no 6-7 pp 514ndash535 2005
[17] G R M Lima C A Montenegro C L F Almeida PF Athayde-Filho J M Barbosa-Filho and L M BatistaldquoDatabase survey of anti-inflammatory plants in South Amer-ica a reviewrdquo International Journal ofMolecular Sciences vol 12no 4 pp 2692ndash2749 2011
[18] K S De Lira Mota G E N Dias M E F Pinto et alldquoFlavonoids with gastroprotective activityrdquo Molecules vol 14no 3 pp 979ndash1012 2009
[19] A L Souto J F Tavares M S da Silva M F F M de Diniz P Fde Athayde-Filho and J M Barbosa Filho ldquoAnti-inflammatoryactivity of alkaloids an update from 2000 to 2010rdquo Moleculesvol 16 no 10 pp 8515ndash8534 2011
[20] F L Silva D C H Fischer J F Tavares M S Silva P Fde Athayde-Filho and J M Barbosa-Filho ldquoCompilation of
secondary metabolites from Bidens pilosa LrdquoMolecules vol 16no 2 pp 1070ndash1102 2011
[21] J R Filho H de Sousa Falcao L M Batista J M B Filho andM R Piuvezam ldquoEffects of plant extracts on HIV-1 proteaserdquoCurrent HIV Research vol 8 no 7 pp 531ndash544 2010
[22] JM Barbosa-Filho A A Alencar X P Nunes et al ldquoSources ofalpha- beta- gamma- delta- and epsilon-carotenes a twentiethcentury reviewrdquo Revista Brasileirta de Farmacogn vol 18 no 1pp 135ndash154 2008
[23] S N S Silva C L F Amaral and T N H Reboucas ldquoAdoptionof conservation practices on farm and selection of varieties byproducers of annatto in the city of Vitoria da Conquista-BArdquoRevista Brasileira de Agroecologica vol 5 pp 106ndash113 2010
[24] A L Bandoni M E Mendiondo R V D Rondina and J DCoussio ldquoSurvey of Argentine medicinal plants I Folklore andphytochemical screeningrdquo Lloydia vol 35 no 1ndash4 pp 69ndash801972
[25] G H Garcia R Campos R A de Torres et al ldquoAntiherpeticactivity of some Argentine medicinal plantsrdquo Fitoterapia vol61 no 6 pp 542ndash546 1990
[26] M G L Brandao T S M Grandi E M M Rocha D RSawyer and A U Krettli ldquoSurvey of medicinal plants used asantimalarials in the Amazonrdquo Journal of Ethnopharmacologyvol 36 no 2 pp 175ndash182 1992
[27] M P Correa Dicionario das Plantas Uteis do Brasil e dasExoticas Cultivadas vol 4 Ministerio da AgriculturaIBDF Riode Janeiro Brasil 1978
[28] G S Hirschmann and A R de Arias ldquoA survey of medicinalplants of minas gerais Brazilrdquo Journal of Ethnopharmacologyvol 29 no 2 pp 159ndash172 1990
[29] R Otero R Fonnegra S L Jimenez et al ldquoSnakebites andethnobotany in the northwest region of Colombia Part Itraditional use of plantsrdquo Journal of Ethnopharmacology vol 71no 3 pp 493ndash504 2000
[30] H Garcia-Barriga Flora Medicinal de Colombia vol 2 Univer-sidad Nacional Bogota Colombia 1975
[31] J T Roig y Mesa Plantas Medicinales Aromaticas o Venenosasde Cuba Ministerio de Agricultura Havana Cuba 1945
[32] A Caceres H Menendez E Mendez et al ldquoAntigonorrhoealactivity of plants used inGuatemala for the treatment of sexuallytransmitted diseasesrdquo Journal of Ethnopharmacology vol 48no 2 pp 85ndash88 1995
[33] J A Duke and R V Martinez Amazonian EthnobotanicalDictionary CRC Press Boca Raton Fla USA 1994
[34] V R Ramirez L J Mostacero A E Garcia et al VegetalesEmpleados enMedicina Tradicional Norperuana Banco Agrariodel Peru Universidad Nacional de Trujillo Trujillo Peru 1988
[35] R Villar J M Calleja C Morales and A Caceres ldquoScreeningof 17 Guatemalan medicinal plants for platelet antiaggregantactivityrdquo Phytotherapy Research vol 11 pp 441ndash445 1997
[36] L M Giron V Freire A Alonzo and A Caceres ldquoEthnob-otanical survey of the medicinal flora used by the Caribs ofGuatemalardquo Journal of Ethnopharmacology vol 34 no 2-3 pp173ndash187 1991
[37] D L Lentz ldquoMedicinal and other economic plants of the PayaofHondurasrdquo Economic Botany vol 47 no 4 pp 358ndash370 1993
[38] D L Lentz A M Clark C D Hufford et al ldquoAntimi-crobial properties of Honduran medicinal plantsrdquo Journal ofEthnopharmacology vol 63 no 3 pp 253ndash263 1998
[39] E Y Morrison and M E West ldquoThe effect of Bixa orellana(Annatto) on blood sugar levels in the anaesthetized dogrdquoWestIndian Medical Journal vol 34 no 1 pp 38ndash42 1985
10 The Scientific World Journal
[40] F G Coe and G J Anderson ldquoScreening of medicinal plantsused by the Garıfuna of eastern Nicaragua for bioactive com-poundsrdquo Journal of Ethnopharmacology vol 53 no 1 pp 29ndash501996
[41] B Barrett ldquoMedicinal plants of Nicaraguarsquos Atlantic CoastrdquoEconomic Botany vol 48 no 1 pp 8ndash20 1994
[42] G Schmeda-Hirschmann and A R de Arias ldquoA screeningmethod for natural products on triatomine bugsrdquo PhytotherapyResearch vol 6 no 2 pp 68ndash73 1992
[43] G E Simpson ldquoFolk medicine in Trinidadrdquo The Journal ofAmerican Folklore vol 75 no 298 pp 326ndash340 1962
[44] D Mahabir and M C Gulliford ldquoUse of medicinal plants fordiabetes in Trinidad and Tobagordquo Revista Panamericana deSalud Publica vol 1 no 3 pp 174ndash179 1997
[45] E S Ayensu ldquoMedicinal plants of theWest IndiesrdquoUnpublishedManuscript 1978
[46] A Z Mercadante A Steck D Rodriguez-Amaya H Pfanderand G Britton ldquoIsolation of methyl 91015840Z-APO-61015840-lycopenoatefrom Bixa Orellanardquo Phytochemistry vol 41 no 4 pp 1201ndash1203 1996
[47] E Angelucci H K Arima E A Kumagai and I AnnattoldquoPreliminary data of the chemical compositionrdquo Coletanea doInstituto de Tecnologia de Alimentos vol 11 pp 89ndash96 1980
[48] A S L Tirimanna ldquoStudy of the carotenoid pigments of Bixaorellana L Seeds by thin layer chromatographyrdquo MikrochimicaActa vol 76 no 1-2 pp 11ndash16 1981
[49] J M Barbosa-Filho R N Silva-Filho B F Lira et al ldquoTeor debixina em quatro variedades de Bixa orellana L cultivadas naParaıbardquo Revista Brasileira de Farmacognosia vol 7-8 pp 41ndash47 1998
[50] A Z Mercadante A Steck and H Pfander ldquoIsolation andstructure elucidation of minor carotenoids from annatto (Bixaorellana L) seedsrdquo Phytochemistry vol 46 no 8 pp 1379ndash13831997
[51] C Prentice-Hernandez and O Rusig ldquoAnnatto (Bixa orellanaL) extract obtained using ethyl alcohol as a solventrdquo Arquivosde Biologia e Tecnologia vol 35 pp 63ndash74 1992
[52] A Z Mercadante ldquoComposition of carotenoids from annattordquoACS Symposium Series vol 775 pp 92ndash101 2001
[53] M J Scotter L A Wilson G P Appleton and L CastleldquoAnalysis of Annatto (Bixa orellana) Food Coloring Formula-tions 1 Determination of Coloring Components and ColoredThermal Degradation Products by High-Performance LiquidChromatography with Photodiode Array Detectionrdquo Journal ofAgricultural and Food Chemistry vol 46 no 3 pp 1031ndash10381998
[54] A J Degnan J H von Elbe and R W Hartel ldquoExtraction ofannatto seed pigment by supercritical carbon dioxiderdquo Journalof Food Science vol 56 pp 1655ndash1659 1991
[55] A ZMercadante A Steck andH Pfander ldquoIsolation and iden-tification of new apocarotenoids from annatto (Bixa orellana)seedsrdquo Journal of Agricultural and Food Chemistry vol 45 no4 pp 1050ndash1054 1997
[56] S G Anderson M G Nair A Chandra and E MorrisonldquoSupercritical fluid carbon dioxide extraction of annatto seedsand quantification of trans-bixin by high pressure liquid chro-matographyrdquo Phytochemical Analysis vol 8 pp 247ndash249 1997
[57] J M Barbosa-Filho Bixa orellana Retrospectiva de usos pop-ulares atividades biologicas fitoquımica e emprego na fito-cosmetica no continente americano Simposio Brasileiro doUrucummdashSIMBRAU Joao Pessoa Brazil 2006
[58] J Revilla Plantas da Amazonia Oportunidades Economicas eSustentaveis Manaus Programa de Desenvolvimento Empre-sarial e Tecnologico 2nd edition 2001
[59] F Oliveira G Akisue and M K Akisue FarmacognosiaAtheneu Sao Paulo Brazil 1996
[60] J Alonso Tratado de Fitofarmacos y Nutraceuticos CorpusRosario Argentina 2004
[61] C O Franco E G Fabri M Barreiro Neto M H Manfiolli MN C Harder and N C Rucker Urucum Sistema de Producaopara o Brasil Emepa-Pb Apta Joao Pessoa Brazil 2008
[62] P A Venugopalan G A Giridhar and A G RavishankarldquoFood Ethanobotanical and diversified applications of Bixaorellana L a scope for its improvement through biotechnolog-ical mediationrdquo Indian Journal of Fundamental and Applied LifeSciences vol 1 pp 9ndash31 2011
[63] L Taylor Herbal Secrets of the Rainforest Sage Press RocklinCalif USA 2nd edition 2002
[64] J S Oliveira Caracterizacao Extracao e Purificacao por Cro-matografia de Compostos de Urucum (Bixa orellana L) [tesisdoctoral en Ingenierıa Quımic] Universidade Federal de SantaCatarina Florianopolis Brazil 2005
[65] A Z Mercadante A Steck and H Pfander ldquoThree minorcarotenoids from annatto (Bixa orellana) seedsrdquo Phytochem-istry vol 52 no 1 pp 135ndash139 1999
[66] V Galindo-Cuspinera M B Lubran and S A Rankin ldquoCom-parison of volatile compounds in water- and oil-soluble annatto(Bixa orellana L) extractsrdquo Journal of Agricultural and FoodChemistry vol 50 no 7 pp 2010ndash2015 2002
[67] R O Alves de Lima L Azevedo L R Ribeiro and D M FSalvadori ldquoStudy on the mutagenicity and antimutagenicity ofa natural food colour (annatto) in mouse bone marrow cellsrdquoFood and Chemical Toxicology vol 41 no 2 pp 189ndash192 2003
[68] L R P Lima T T Oliveira T J Nagem et al ldquoBixina norbixinae quercetina e seus efeitos no metabolismo lipıdico de coelhosrdquoBrazilian Journal of Veterinary Research andAnimal Science vol38 pp 196ndash200 2001
[69] J D Fontana S V Mendes D S Persike L F Peracetta andM Passos ldquoCarotenoides cores atraentes e acao biologicardquoBiotecnologia Ciencia amp Desenvolvimento vol 2 p 13 2000
[70] C A Penna M Radice G O Gutkind et al ldquoAntibacterial andantifungal activities of some Argentinean plantsrdquo Fitoterapiavol 65 no 2 pp 172ndash174 1994
[71] A M Broussalis G E Ferraro V S Martino R Pinzon J DCoussio and J C Alvarez ldquoArgentine plants as potential sourceof insecticidal compoundsrdquo Journal of Ethnopharmacology vol67 no 2 pp 219ndash223 1999
[72] A Rojas de Arias G Schmeda-Hirschmann and A FalcaoldquoFeeding deterrency and insecticidal effects of plant extracts onLutzomyia longipalpisrdquo Phytotherapy Research vol 6 no 2 pp64ndash67 1992
[73] M S Pinheiro and M Z Rouquayrol ldquoMolluscicidal activityof plants from Northeast Brazilrdquo Revista Brasileira de PesquisasMedicas e Biologicas vol 7 pp 389ndash394 1974
[74] A Hagiwara N Imai T Ichihara et al ldquoA thirteen-week oraltoxicity study of annatto extract (norbixin) a natural food colorextracted from the seed coat of annatto (Bixa orellana L) inSprague-Dawley ratsrdquoFood andChemical Toxicology vol 41 no8 pp 1157ndash1164 2003
[75] C R Almeida R B Silva M J Marques and J K ChavascoldquoEvaluation of antiparasitic activity of hydroethanolic extractsfrom root stem and leaf of Bixa orellana L on Leishmania
The Scientific World Journal 11
amazonensis samplesrdquo Revista da Universidade Vale do RioVerde vol 10 no 2 pp 384ndash391 2012
[76] M V Lopes V C Desoti A D O Caleare T Ueda-NakamuraS O Silva and C V Nakamura ldquoMitochondria superoxideanion production contributes to geranylgeraniol-induced deathin leishmania amazonensisrdquo Evidence-Based Complementaryand Alternative Medicine vol 2012 Article ID 298320 9 pages2012
[77] J M Ferreira D F Sousa M B Dantas et al ldquoEffects of BixaorellanaL seeds onhyperlipidemiardquoPhytotherapyResearch vol27 no 1 pp 144ndash147 2013
[78] P S BenoitHH S FongGH Svoboda andN R FarnsworthldquoBiological and phytochemical evaluation of plants XIV Anti-inflammatory evaluation of 163 species of plantsrdquo Lloydia vol39 no 2-3 pp 160ndash171 1976
[79] D Carabajal A Casaco L Arruzazabala R Gonzalez andV Fuentes ldquoPharmacological screening of plant decoctionscommonly used in Cuban folk medicinerdquo Journal of Ethnophar-macology vol 33 no 1-2 pp 21ndash24 1991
[80] A F C Valdes J M Martınez D A Rodrıguez R S Lizamaand Y G Gaiten ldquoActividad antimalarica de un extractohidroalcoholico de Bixa orellanaLrdquo Revista Cubana de Medic-ina Tropical vol 63 pp 181ndash185 2011
[81] A D Garcıa H R Sanchez and R S Lizama ldquoCitotoxicidadde extractos de plantas medicinales sobre la lınea celularde carcinoma de pulmon humano A549rdquo Revista Cubana deFarmacia vol 45 pp 101ndash108 2011
[82] B Freixa R Vila L Vargas N Lozano T Adzet and SCanigueral ldquoScreening for antifungal activity of nineteen LatinAmerican plantsrdquo Phytotherapy Research vol 12 no 6 pp 427ndash430 1998
[83] A Caceres B Lopez S Gonzalez I Berger I Tada and JMaki ldquoPlants used in Guatemala for the treatment of pro-tozoal infections I Screening of activity to bacteria fungiand American trypanosomes of 13 native plantsrdquo Journal ofEthnopharmacology vol 62 no 3 pp 195ndash202 1998
[84] A Caceres O Cano B Samayoa and L Aguilar ldquoPlants usedin Guatemala for the treatment of gastrointestinal disorders1 Screening of 84 plants against enterobacteriardquo Journal ofEthnopharmacology vol 30 no 1 pp 55ndash73 1990
[85] A S Matsui S Hoskin M Kashiwagi et al ldquoA survey ofnatural products from Hawaii and other areas of the Pacificfor an antifertility effect in micerdquo Internationale Zeitschrift furKlinische PharmakologieTherapie und Toxikologie vol 5 no 1pp 65ndash69 1971
[86] M Abayomi A S Adebayo D Bennett R Porter and JS Campbell ldquoIn vitro antioxidant activity of Bixa orellana(Annatto) seed extractrdquo Journal of Applied PharmaceuticalScience vol 4 no 2 pp 101ndash106 2014
[87] NW Dunham and K R Allard ldquoA preliminary pharmacologicinvestigation of the roots of Bixa orellanardquo Journal of theAmerican Pharmacist Associantion vol 49 pp 218ndash219 1960
[88] F RMedina andRWoodbury ldquoTerrestrial plantsmolluscicidalto lymnaeid hosts of Fasciliasis hepatica in Puerto Ricordquo Journalof Agricultura of the University of Puerto Rico vol 63 pp 366ndash376 1979
[89] B Weniger Y Jiang A Oulad-Ali L Italiano J P Beck and RAnton ldquoBiological effects of bixin and Bixa orellana extracts onlymphoid cells in culturerdquo Planta Medica vol 59 no 7 articleA680 1993
[90] CM Chariandy C E Seaforth R H Phelps G V Pollard andB P S Khambay ldquoScreening of medicinal plants from Trinidad
and Tobago for antimicrobial and insecticidal propertiesrdquoJournal of Ethnopharmacology vol 64 no 3 pp 265ndash270 1999
[91] F J R Paumgartten R R Carvalho I B Araujo et alldquoEvaluation of the developmental toxicity of annatto in the ratrdquoFood and Chemical Toxicology vol 40 no 11 pp 1595ndash16012002
[92] C F Spencer F R Koniuszy E F Rogers et al ldquoSurvey of plantsfor antimalarial activityrdquo Lloydia vol 10 no 3 pp 145ndash174 1947
[93] H Mikkelsen J C Larsen and F Tarding ldquoHypersensitivityreactions to food colours with special reference to the naturalcolour annatto extract (butter colour)rdquo Toxicological Aspects ofFood Safety vol 1 pp 141ndash143 1978
Submit your manuscripts athttpwwwhindawicom
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Hindawi Publishing Corporationhttpwwwhindawicom
Volume 2014
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VaccinesJournal of
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Advances in Pharmacological Sciences
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
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Pharmaceutics
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
The Scientific World Journal 7
Table3Con
tinued
Cou
ntry
biologicalactiv
ityPartused
Type
ofextract
Organism
teste
dMod
elteste
dDoseu
sed
Activ
ityRe
ferences
Guatemala
Antibacteria
lLE
Vario
usEscherich
iacoli
Invitro
50120583Ldisk
Inactiv
e[83]
Pseudomonas
aeruginosa
Invitro
MICgt10mgmL
Inactiv
e[83]
Salm
onellatyphi
Invitro
MICgt10mgmL
Inactiv
e[83]
Shigelladysenteriae
Invitro
50120583L
Inactiv
e[83]
Staphylococcus
aureus
Invitro
MICgt10mgmL
Inactiv
e[83]
Antifu
ngal
LEH
2OAspergillus
flavus
Invitro
MICgt10mgmL
Inactiv
e[84]
Cand
idaalbicans
Invitro
MICgt10mgmL
Inactiv
e[84]
Microsporum
gypseum
Invitro
MICgt10mgmL
Inactiv
e[84]
Antigon
orrheal
LEEtOH
Neisseriagonorrhea
Invitro
50120583Ldisk
Activ
e[32]
Antitrypanosom
alLE
EtOH
Trypanosom
acruzi
Invitro
MICgt1m
gmL
Inactiv
e[83]
Cytotoxic
LEH
2OCr
ustacean
Artemiasalin
aLC
50gt10
00pp
mInactiv
e[83]
Inhibof
plateletaggregation
SE
Invitro
Thrombinaggregation
IC50
0795m
gmL
Inactiv
e[35]
Haw
aii
Con
traceptiv
eRO
Mou
se
02m
Lanim
alInactiv
e[85]
Jamaica
Hypoglycemic
SECH
Cl3
Dog
1gAc
tive
[39]
H2O
Dog
200m
Lanim
alAc
tive
[39]
Antioxidant
SEEtOH
Invitro
Invitro
025
and25120583
gmL
Activ
e[86]
Mexico
Allergenic
SEOil
Hum
an25120583L
person
Activ
e[87]
Paragu
ayInsecticidal
SEPetr
ether
Insect
Rhodnius
negle
ctus
50120583g
Inactiv
e[42]
Puerto
Rico
Molluscicidal
TPH
2OCon
chLymna
eacubensis
LD100gt1M
ppm
Inactiv
e[88]
Dom
inican
Repu
blic
Cytotoxic
SEEtOH
Cellculture
Molt4
cells
200120583
gmL
Inactiv
e[89]
Trinidad
andTo
bago
Antibacteria
lSE
EtOAc
Escherich
iacoli
Invitro
1000120583gmL
Inactiv
e[90]
Pseudomonas
aeruginosa
Invitro
1000120583gmL
Inactiv
e[90]
USA A
nticon
vulsa
ntRA
EtOH
Mou
seSeizureselectroshock
100m
gkg
Inactiv
e[91]
Rat
Seizurespentylenetetrazole
400m
gkg
Inactiv
e[91]
Antim
alarial
SECH
Cl3
Chicken
Plasmodium
gallina
ceum
388m
gkg
Inactiv
e[92]
Mutagenic
SEMeO
HSalm
onellatyphim
urium
100m
gplaque
Inactiv
e[93]
H2O
Invitro
Placentaltroph
oblasts
100m
gplaque
Inactiv
e[93]
Hypotensiv
eRA
EtOH
Rat
50mgkg
Activ
e[93]
Toxicity
RAH
2OMou
seLD
50gt700m
gkg
Inactiv
e[92]
LEleafAP
aeria
lpartTP
totalplantRO
roo
tSE
seedno
tgivenLD5050
lethaldo
seIC5
0concentrationthatinhibits50of
thee
ffectM
ICm
inim
uminhibitory
concentration
8 The Scientific World Journal
on the dose that is administered The failure to require in-depth data related to toxicological and chemical analysesfor the registration of food additives derived from naturalsources [67 74] certainly makes the information aboutpossible unwanted effects andor pharmacological activitiesresulting from their use much rarer than expected in view ofthe importance of the topic In Brazil the use of annatto is sowidespread that its safety is not even questioned
Paumgartten et al [91] evaluated the toxicity of annattoextracts in rats Doses up to 500mgkg body weightdaywere introduced directly into the stomach of pregnant ratsto evaluate the effect on the mother and fetus and noadverse effects were found for either The annatto extract didnot induce an increase in the incidence of visible externalvisceral or skeletal anomalies in the fetuses Therefore thestudy suggested that the annatto extract was not toxic to ratsnor was it embryotoxic Studies performed in Brazil by Alvesde Lima et al [67] where extracts of annatto weremixed withthe food of male rats showed that the concentrations testedhad no mutagenic or antimutagenic activity in their bonemarrow cells A parallel toxicity study conducted byHagiwaraet al [74] showed that 01 annatto extract administered forthirteen weeks in the feed of male and female rats did notshow any adverse effects However when higher doses wereadministered (03 and 09) the authors noticed an increasein liver weight as well as changes in blood chemistriesincluding increase in alkaline phosphatase phospholipidsand total protein as well as albumin and albuminglobulinratio
Hagiwara et al [74] also evaluated extracts of annattofor liver carcinogenicity in rats and found no evidence ofliver tumors even when given to animals at a high dose of200mgkg body weightday compared to an acceptable doseof 00 to 0065mgkgday thus indicating that the dangerof a hepatocarcinogenic effect in humans may be absent ornegligible
A toxicity test was performedwith extracts obtained fromboth plant seeds and shoots and no significant effect wasobserved The experiments were performed in the UnitedStates using mice as the animal model and it was found thatthe LD50 was greater than 700mgkg [92]
9 Correlation between the BiologicalActivities Phytochemistry and theTraditional Uses of Bixa orellana
Table 1 shows that many of the traditional uses of Bixaorellana are the same in several countries of South andCentral America which suggests its effectiveness as a ther-apeutic agent Extracts of Bixa orellana showed biologicalactivities such as antioxidant hypotensive molluscicideand antimalarial against A549 cells for carcinoma of thelung allergy hypoglycemic antifungal antioxidant insectrepellent antigonococcal and antivenom serum and some ofthem are in accordance with the traditional use for examplein Brazil it is used to extract the seeds with purpose repellentinsecticide and antimalaria and scientific studies in the samecountrywith the Lutzomyia longipalpis insect repellent action
and prove a study in Cuba proved the pharmacological actionfor antimalarial activity when tested against Plasmodiumberghei Some of them are in accordance with the traditionaluse for example seed extracts have been used in Brazil andCuba as insect repellent and antimalarial Antioxidant andinsect repellent activities can be attributed to the carotenoidsand the essential and fixed oils respectively
Despite the previous reports about the presence of com-ponents with anti-inflammatory properties such as salicylicacid lutein polyphenols and tannins this activity has not yetbeen proven for Bixa orellana extracts Similarly the plantrsquosessential and fixed oils have shown antibacterial propertiesalthough this activity has not been proven too
In general the data obtained in this review do not allowcorrelations between the biologic activities tested in vitro or invivo with the compounds identified in this species Howevertaking into account the related activities such as the antipara-sitic effect and the lack of mutagenic and cytotoxicity activityit is possible to consider Bixa orellana as a potential source forthe development of phytopharmaceutical products
In conclusion the studies discussed in this review repre-sent a rich database around the Bixa orellana activities andits potential uses which evokes the feasibility of phytophar-maceuticals to treat some diseases whenever an antioxidanthypotensor or hypoglycemiant activity is necessary
Although the commercial exploitation of this species iswell established there are very few studies on its pharma-cological effects Considering the need for developing a safeand effective product more studies should be performed inorder to confirm other biological activities supported by thepopular uses of Bixa orellana
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors are grateful to CNPqPRONEXFAPESQ andCAPES for financial support and to the NAPRALERTDatabase of the University of Illinois USA for the literatureon Bixa orellana A Leyva helped in editing the Englishlanguage of the paper
References
[1] M B Perecin O A Bovi and N B Maia ldquoPesquisa complantas aromaticas medicinais corantes o papel do InstitutoAgronomicordquo O Agronomico vol 54 pp 21ndash24 2002
[2] M E A Elias G Schroth J L V Macedo M S S Motaand S A DrsquoAngelo ldquoMineral nutrition growth and yields ofannatto trees (Bixa orellana) in agroforestry on an AmazonianFerralsolrdquo Experimental Agriculture vol 38 no 3 pp 277ndash2892002
[3] A R R Bastos J G Carvalho R P Assis and A B C FilholdquoMarcha de absorcao de nutrientes em urucum ( Bixa orellanaL) tipo cultivado piave vermelha em fase de viveirordquoCerne vol5 pp 76ndash85 1999
The Scientific World Journal 9
[4] E PThomasM Colvin S B Rosen C Zuccarini and S PetzerldquoHIV prevalence study and costing analysis undertaken for thedevelopment of an HIVAIDS workplace strategy for buffalocity municipalityrdquo Tech Rep Medical Research Council Buf-falo NY USA 2005
[5] C F Franco ldquoO Agronegocio do urucum na regiao Nordesterdquo 1Reuniao Nacional da Cadeia Produtiva de Urucum CD-Rom2007
[6] A Giorgi P De Marinis G Granelli L M Chiesa and SPanseri ldquoSecondary metabolite profile antioxidant capacityand mosquito repellent activity of Bixa orellana from BrazilianAmazon regionrdquo Journal of Chemistry vol 2013 Article ID409826 10 pages 2013
[7] J S Silva M D Moura R A G Oliveira M F F Dinizand J M Barbosa-Filho ldquoNatural product inhibitors of ovarianneoplasiardquo Phytomedicine vol 10 no 2-3 pp 221ndash232 2003
[8] F C F Sousa C T V Melo C O M Cito et al ldquoPlantasmedicinais e seus constituintes bioativos uma revisao dabioatividade e potenciais benefıcios nos disturbios da ansiedadeem modelos animaisrdquo Revista Brasileira de Farmacognosia vol18 pp 642ndash654 2008
[9] L J Quintans Jr J R G S Almeida J T Lima et al ldquoPlantswith anticonvulsant propertiesmdasha reviewrdquo Revista Brasileira deFarmacognosia vol 18 pp 798ndash819 2008
[10] HD S Falcao J A Leite JM Barbosa-Filho et al ldquoGastric andduodenal antiulcer activity of alkaloids a reviewrdquoMolecules vol13 no 12 pp 3198ndash3223 2008
[11] H S Falcao I R Mariath M F F M Diniz L M Batista andJ M Barbosa-Filho ldquoPlants of the American continent withantiulcer activityrdquo Phytomedicine vol 15 no 1-2 pp 132ndash1462008
[12] I R Mariath H D S Falcao J M Barbosa-Filho et al ldquoPlantsof the American continent with antimalarial activityrdquo RevistaBrasileira de Farmacognosia vol 19 no 1 pp 158ndash192 2009
[13] J E R Hon P M Soares C L Melo et al ldquoAtividadefarmacologica da monocrotalina isolada de plantas do generoCrotalariardquo Revista Brasileira de Farmacognosia vol 20 pp453ndash458 2010
[14] R N Almeida D S Navarro and J M Barbosa-Filho ldquoPlantswith central analgesic activityrdquo Phytomedicine vol 8 no 4 pp310ndash322 2001
[15] N Z T Jesus H S Falcao I F Gomes et al ldquoTanninspeptic ulcers and related mechanismsrdquo International Journal ofMolecular Sciences vol 13 no 3 pp 3203ndash3228 2012
[16] L G Rocha J R G S Almeida R O Macedo and J MBarbosa-Filho ldquoA review of natural products with antileishma-nial activityrdquo Phytomedicine vol 12 no 6-7 pp 514ndash535 2005
[17] G R M Lima C A Montenegro C L F Almeida PF Athayde-Filho J M Barbosa-Filho and L M BatistaldquoDatabase survey of anti-inflammatory plants in South Amer-ica a reviewrdquo International Journal ofMolecular Sciences vol 12no 4 pp 2692ndash2749 2011
[18] K S De Lira Mota G E N Dias M E F Pinto et alldquoFlavonoids with gastroprotective activityrdquo Molecules vol 14no 3 pp 979ndash1012 2009
[19] A L Souto J F Tavares M S da Silva M F F M de Diniz P Fde Athayde-Filho and J M Barbosa Filho ldquoAnti-inflammatoryactivity of alkaloids an update from 2000 to 2010rdquo Moleculesvol 16 no 10 pp 8515ndash8534 2011
[20] F L Silva D C H Fischer J F Tavares M S Silva P Fde Athayde-Filho and J M Barbosa-Filho ldquoCompilation of
secondary metabolites from Bidens pilosa LrdquoMolecules vol 16no 2 pp 1070ndash1102 2011
[21] J R Filho H de Sousa Falcao L M Batista J M B Filho andM R Piuvezam ldquoEffects of plant extracts on HIV-1 proteaserdquoCurrent HIV Research vol 8 no 7 pp 531ndash544 2010
[22] JM Barbosa-Filho A A Alencar X P Nunes et al ldquoSources ofalpha- beta- gamma- delta- and epsilon-carotenes a twentiethcentury reviewrdquo Revista Brasileirta de Farmacogn vol 18 no 1pp 135ndash154 2008
[23] S N S Silva C L F Amaral and T N H Reboucas ldquoAdoptionof conservation practices on farm and selection of varieties byproducers of annatto in the city of Vitoria da Conquista-BArdquoRevista Brasileira de Agroecologica vol 5 pp 106ndash113 2010
[24] A L Bandoni M E Mendiondo R V D Rondina and J DCoussio ldquoSurvey of Argentine medicinal plants I Folklore andphytochemical screeningrdquo Lloydia vol 35 no 1ndash4 pp 69ndash801972
[25] G H Garcia R Campos R A de Torres et al ldquoAntiherpeticactivity of some Argentine medicinal plantsrdquo Fitoterapia vol61 no 6 pp 542ndash546 1990
[26] M G L Brandao T S M Grandi E M M Rocha D RSawyer and A U Krettli ldquoSurvey of medicinal plants used asantimalarials in the Amazonrdquo Journal of Ethnopharmacologyvol 36 no 2 pp 175ndash182 1992
[27] M P Correa Dicionario das Plantas Uteis do Brasil e dasExoticas Cultivadas vol 4 Ministerio da AgriculturaIBDF Riode Janeiro Brasil 1978
[28] G S Hirschmann and A R de Arias ldquoA survey of medicinalplants of minas gerais Brazilrdquo Journal of Ethnopharmacologyvol 29 no 2 pp 159ndash172 1990
[29] R Otero R Fonnegra S L Jimenez et al ldquoSnakebites andethnobotany in the northwest region of Colombia Part Itraditional use of plantsrdquo Journal of Ethnopharmacology vol 71no 3 pp 493ndash504 2000
[30] H Garcia-Barriga Flora Medicinal de Colombia vol 2 Univer-sidad Nacional Bogota Colombia 1975
[31] J T Roig y Mesa Plantas Medicinales Aromaticas o Venenosasde Cuba Ministerio de Agricultura Havana Cuba 1945
[32] A Caceres H Menendez E Mendez et al ldquoAntigonorrhoealactivity of plants used inGuatemala for the treatment of sexuallytransmitted diseasesrdquo Journal of Ethnopharmacology vol 48no 2 pp 85ndash88 1995
[33] J A Duke and R V Martinez Amazonian EthnobotanicalDictionary CRC Press Boca Raton Fla USA 1994
[34] V R Ramirez L J Mostacero A E Garcia et al VegetalesEmpleados enMedicina Tradicional Norperuana Banco Agrariodel Peru Universidad Nacional de Trujillo Trujillo Peru 1988
[35] R Villar J M Calleja C Morales and A Caceres ldquoScreeningof 17 Guatemalan medicinal plants for platelet antiaggregantactivityrdquo Phytotherapy Research vol 11 pp 441ndash445 1997
[36] L M Giron V Freire A Alonzo and A Caceres ldquoEthnob-otanical survey of the medicinal flora used by the Caribs ofGuatemalardquo Journal of Ethnopharmacology vol 34 no 2-3 pp173ndash187 1991
[37] D L Lentz ldquoMedicinal and other economic plants of the PayaofHondurasrdquo Economic Botany vol 47 no 4 pp 358ndash370 1993
[38] D L Lentz A M Clark C D Hufford et al ldquoAntimi-crobial properties of Honduran medicinal plantsrdquo Journal ofEthnopharmacology vol 63 no 3 pp 253ndash263 1998
[39] E Y Morrison and M E West ldquoThe effect of Bixa orellana(Annatto) on blood sugar levels in the anaesthetized dogrdquoWestIndian Medical Journal vol 34 no 1 pp 38ndash42 1985
10 The Scientific World Journal
[40] F G Coe and G J Anderson ldquoScreening of medicinal plantsused by the Garıfuna of eastern Nicaragua for bioactive com-poundsrdquo Journal of Ethnopharmacology vol 53 no 1 pp 29ndash501996
[41] B Barrett ldquoMedicinal plants of Nicaraguarsquos Atlantic CoastrdquoEconomic Botany vol 48 no 1 pp 8ndash20 1994
[42] G Schmeda-Hirschmann and A R de Arias ldquoA screeningmethod for natural products on triatomine bugsrdquo PhytotherapyResearch vol 6 no 2 pp 68ndash73 1992
[43] G E Simpson ldquoFolk medicine in Trinidadrdquo The Journal ofAmerican Folklore vol 75 no 298 pp 326ndash340 1962
[44] D Mahabir and M C Gulliford ldquoUse of medicinal plants fordiabetes in Trinidad and Tobagordquo Revista Panamericana deSalud Publica vol 1 no 3 pp 174ndash179 1997
[45] E S Ayensu ldquoMedicinal plants of theWest IndiesrdquoUnpublishedManuscript 1978
[46] A Z Mercadante A Steck D Rodriguez-Amaya H Pfanderand G Britton ldquoIsolation of methyl 91015840Z-APO-61015840-lycopenoatefrom Bixa Orellanardquo Phytochemistry vol 41 no 4 pp 1201ndash1203 1996
[47] E Angelucci H K Arima E A Kumagai and I AnnattoldquoPreliminary data of the chemical compositionrdquo Coletanea doInstituto de Tecnologia de Alimentos vol 11 pp 89ndash96 1980
[48] A S L Tirimanna ldquoStudy of the carotenoid pigments of Bixaorellana L Seeds by thin layer chromatographyrdquo MikrochimicaActa vol 76 no 1-2 pp 11ndash16 1981
[49] J M Barbosa-Filho R N Silva-Filho B F Lira et al ldquoTeor debixina em quatro variedades de Bixa orellana L cultivadas naParaıbardquo Revista Brasileira de Farmacognosia vol 7-8 pp 41ndash47 1998
[50] A Z Mercadante A Steck and H Pfander ldquoIsolation andstructure elucidation of minor carotenoids from annatto (Bixaorellana L) seedsrdquo Phytochemistry vol 46 no 8 pp 1379ndash13831997
[51] C Prentice-Hernandez and O Rusig ldquoAnnatto (Bixa orellanaL) extract obtained using ethyl alcohol as a solventrdquo Arquivosde Biologia e Tecnologia vol 35 pp 63ndash74 1992
[52] A Z Mercadante ldquoComposition of carotenoids from annattordquoACS Symposium Series vol 775 pp 92ndash101 2001
[53] M J Scotter L A Wilson G P Appleton and L CastleldquoAnalysis of Annatto (Bixa orellana) Food Coloring Formula-tions 1 Determination of Coloring Components and ColoredThermal Degradation Products by High-Performance LiquidChromatography with Photodiode Array Detectionrdquo Journal ofAgricultural and Food Chemistry vol 46 no 3 pp 1031ndash10381998
[54] A J Degnan J H von Elbe and R W Hartel ldquoExtraction ofannatto seed pigment by supercritical carbon dioxiderdquo Journalof Food Science vol 56 pp 1655ndash1659 1991
[55] A ZMercadante A Steck andH Pfander ldquoIsolation and iden-tification of new apocarotenoids from annatto (Bixa orellana)seedsrdquo Journal of Agricultural and Food Chemistry vol 45 no4 pp 1050ndash1054 1997
[56] S G Anderson M G Nair A Chandra and E MorrisonldquoSupercritical fluid carbon dioxide extraction of annatto seedsand quantification of trans-bixin by high pressure liquid chro-matographyrdquo Phytochemical Analysis vol 8 pp 247ndash249 1997
[57] J M Barbosa-Filho Bixa orellana Retrospectiva de usos pop-ulares atividades biologicas fitoquımica e emprego na fito-cosmetica no continente americano Simposio Brasileiro doUrucummdashSIMBRAU Joao Pessoa Brazil 2006
[58] J Revilla Plantas da Amazonia Oportunidades Economicas eSustentaveis Manaus Programa de Desenvolvimento Empre-sarial e Tecnologico 2nd edition 2001
[59] F Oliveira G Akisue and M K Akisue FarmacognosiaAtheneu Sao Paulo Brazil 1996
[60] J Alonso Tratado de Fitofarmacos y Nutraceuticos CorpusRosario Argentina 2004
[61] C O Franco E G Fabri M Barreiro Neto M H Manfiolli MN C Harder and N C Rucker Urucum Sistema de Producaopara o Brasil Emepa-Pb Apta Joao Pessoa Brazil 2008
[62] P A Venugopalan G A Giridhar and A G RavishankarldquoFood Ethanobotanical and diversified applications of Bixaorellana L a scope for its improvement through biotechnolog-ical mediationrdquo Indian Journal of Fundamental and Applied LifeSciences vol 1 pp 9ndash31 2011
[63] L Taylor Herbal Secrets of the Rainforest Sage Press RocklinCalif USA 2nd edition 2002
[64] J S Oliveira Caracterizacao Extracao e Purificacao por Cro-matografia de Compostos de Urucum (Bixa orellana L) [tesisdoctoral en Ingenierıa Quımic] Universidade Federal de SantaCatarina Florianopolis Brazil 2005
[65] A Z Mercadante A Steck and H Pfander ldquoThree minorcarotenoids from annatto (Bixa orellana) seedsrdquo Phytochem-istry vol 52 no 1 pp 135ndash139 1999
[66] V Galindo-Cuspinera M B Lubran and S A Rankin ldquoCom-parison of volatile compounds in water- and oil-soluble annatto(Bixa orellana L) extractsrdquo Journal of Agricultural and FoodChemistry vol 50 no 7 pp 2010ndash2015 2002
[67] R O Alves de Lima L Azevedo L R Ribeiro and D M FSalvadori ldquoStudy on the mutagenicity and antimutagenicity ofa natural food colour (annatto) in mouse bone marrow cellsrdquoFood and Chemical Toxicology vol 41 no 2 pp 189ndash192 2003
[68] L R P Lima T T Oliveira T J Nagem et al ldquoBixina norbixinae quercetina e seus efeitos no metabolismo lipıdico de coelhosrdquoBrazilian Journal of Veterinary Research andAnimal Science vol38 pp 196ndash200 2001
[69] J D Fontana S V Mendes D S Persike L F Peracetta andM Passos ldquoCarotenoides cores atraentes e acao biologicardquoBiotecnologia Ciencia amp Desenvolvimento vol 2 p 13 2000
[70] C A Penna M Radice G O Gutkind et al ldquoAntibacterial andantifungal activities of some Argentinean plantsrdquo Fitoterapiavol 65 no 2 pp 172ndash174 1994
[71] A M Broussalis G E Ferraro V S Martino R Pinzon J DCoussio and J C Alvarez ldquoArgentine plants as potential sourceof insecticidal compoundsrdquo Journal of Ethnopharmacology vol67 no 2 pp 219ndash223 1999
[72] A Rojas de Arias G Schmeda-Hirschmann and A FalcaoldquoFeeding deterrency and insecticidal effects of plant extracts onLutzomyia longipalpisrdquo Phytotherapy Research vol 6 no 2 pp64ndash67 1992
[73] M S Pinheiro and M Z Rouquayrol ldquoMolluscicidal activityof plants from Northeast Brazilrdquo Revista Brasileira de PesquisasMedicas e Biologicas vol 7 pp 389ndash394 1974
[74] A Hagiwara N Imai T Ichihara et al ldquoA thirteen-week oraltoxicity study of annatto extract (norbixin) a natural food colorextracted from the seed coat of annatto (Bixa orellana L) inSprague-Dawley ratsrdquoFood andChemical Toxicology vol 41 no8 pp 1157ndash1164 2003
[75] C R Almeida R B Silva M J Marques and J K ChavascoldquoEvaluation of antiparasitic activity of hydroethanolic extractsfrom root stem and leaf of Bixa orellana L on Leishmania
The Scientific World Journal 11
amazonensis samplesrdquo Revista da Universidade Vale do RioVerde vol 10 no 2 pp 384ndash391 2012
[76] M V Lopes V C Desoti A D O Caleare T Ueda-NakamuraS O Silva and C V Nakamura ldquoMitochondria superoxideanion production contributes to geranylgeraniol-induced deathin leishmania amazonensisrdquo Evidence-Based Complementaryand Alternative Medicine vol 2012 Article ID 298320 9 pages2012
[77] J M Ferreira D F Sousa M B Dantas et al ldquoEffects of BixaorellanaL seeds onhyperlipidemiardquoPhytotherapyResearch vol27 no 1 pp 144ndash147 2013
[78] P S BenoitHH S FongGH Svoboda andN R FarnsworthldquoBiological and phytochemical evaluation of plants XIV Anti-inflammatory evaluation of 163 species of plantsrdquo Lloydia vol39 no 2-3 pp 160ndash171 1976
[79] D Carabajal A Casaco L Arruzazabala R Gonzalez andV Fuentes ldquoPharmacological screening of plant decoctionscommonly used in Cuban folk medicinerdquo Journal of Ethnophar-macology vol 33 no 1-2 pp 21ndash24 1991
[80] A F C Valdes J M Martınez D A Rodrıguez R S Lizamaand Y G Gaiten ldquoActividad antimalarica de un extractohidroalcoholico de Bixa orellanaLrdquo Revista Cubana de Medic-ina Tropical vol 63 pp 181ndash185 2011
[81] A D Garcıa H R Sanchez and R S Lizama ldquoCitotoxicidadde extractos de plantas medicinales sobre la lınea celularde carcinoma de pulmon humano A549rdquo Revista Cubana deFarmacia vol 45 pp 101ndash108 2011
[82] B Freixa R Vila L Vargas N Lozano T Adzet and SCanigueral ldquoScreening for antifungal activity of nineteen LatinAmerican plantsrdquo Phytotherapy Research vol 12 no 6 pp 427ndash430 1998
[83] A Caceres B Lopez S Gonzalez I Berger I Tada and JMaki ldquoPlants used in Guatemala for the treatment of pro-tozoal infections I Screening of activity to bacteria fungiand American trypanosomes of 13 native plantsrdquo Journal ofEthnopharmacology vol 62 no 3 pp 195ndash202 1998
[84] A Caceres O Cano B Samayoa and L Aguilar ldquoPlants usedin Guatemala for the treatment of gastrointestinal disorders1 Screening of 84 plants against enterobacteriardquo Journal ofEthnopharmacology vol 30 no 1 pp 55ndash73 1990
[85] A S Matsui S Hoskin M Kashiwagi et al ldquoA survey ofnatural products from Hawaii and other areas of the Pacificfor an antifertility effect in micerdquo Internationale Zeitschrift furKlinische PharmakologieTherapie und Toxikologie vol 5 no 1pp 65ndash69 1971
[86] M Abayomi A S Adebayo D Bennett R Porter and JS Campbell ldquoIn vitro antioxidant activity of Bixa orellana(Annatto) seed extractrdquo Journal of Applied PharmaceuticalScience vol 4 no 2 pp 101ndash106 2014
[87] NW Dunham and K R Allard ldquoA preliminary pharmacologicinvestigation of the roots of Bixa orellanardquo Journal of theAmerican Pharmacist Associantion vol 49 pp 218ndash219 1960
[88] F RMedina andRWoodbury ldquoTerrestrial plantsmolluscicidalto lymnaeid hosts of Fasciliasis hepatica in Puerto Ricordquo Journalof Agricultura of the University of Puerto Rico vol 63 pp 366ndash376 1979
[89] B Weniger Y Jiang A Oulad-Ali L Italiano J P Beck and RAnton ldquoBiological effects of bixin and Bixa orellana extracts onlymphoid cells in culturerdquo Planta Medica vol 59 no 7 articleA680 1993
[90] CM Chariandy C E Seaforth R H Phelps G V Pollard andB P S Khambay ldquoScreening of medicinal plants from Trinidad
and Tobago for antimicrobial and insecticidal propertiesrdquoJournal of Ethnopharmacology vol 64 no 3 pp 265ndash270 1999
[91] F J R Paumgartten R R Carvalho I B Araujo et alldquoEvaluation of the developmental toxicity of annatto in the ratrdquoFood and Chemical Toxicology vol 40 no 11 pp 1595ndash16012002
[92] C F Spencer F R Koniuszy E F Rogers et al ldquoSurvey of plantsfor antimalarial activityrdquo Lloydia vol 10 no 3 pp 145ndash174 1947
[93] H Mikkelsen J C Larsen and F Tarding ldquoHypersensitivityreactions to food colours with special reference to the naturalcolour annatto extract (butter colour)rdquo Toxicological Aspects ofFood Safety vol 1 pp 141ndash143 1978
Submit your manuscripts athttpwwwhindawicom
PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom
Volume 2014
ToxinsJournal of
VaccinesJournal of
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
AntibioticsInternational Journal of
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StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Drug DeliveryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in Pharmacological Sciences
Tropical MedicineJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
AddictionJournal of
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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
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Autoimmune Diseases
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Pharmaceutics
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
8 The Scientific World Journal
on the dose that is administered The failure to require in-depth data related to toxicological and chemical analysesfor the registration of food additives derived from naturalsources [67 74] certainly makes the information aboutpossible unwanted effects andor pharmacological activitiesresulting from their use much rarer than expected in view ofthe importance of the topic In Brazil the use of annatto is sowidespread that its safety is not even questioned
Paumgartten et al [91] evaluated the toxicity of annattoextracts in rats Doses up to 500mgkg body weightdaywere introduced directly into the stomach of pregnant ratsto evaluate the effect on the mother and fetus and noadverse effects were found for either The annatto extract didnot induce an increase in the incidence of visible externalvisceral or skeletal anomalies in the fetuses Therefore thestudy suggested that the annatto extract was not toxic to ratsnor was it embryotoxic Studies performed in Brazil by Alvesde Lima et al [67] where extracts of annatto weremixed withthe food of male rats showed that the concentrations testedhad no mutagenic or antimutagenic activity in their bonemarrow cells A parallel toxicity study conducted byHagiwaraet al [74] showed that 01 annatto extract administered forthirteen weeks in the feed of male and female rats did notshow any adverse effects However when higher doses wereadministered (03 and 09) the authors noticed an increasein liver weight as well as changes in blood chemistriesincluding increase in alkaline phosphatase phospholipidsand total protein as well as albumin and albuminglobulinratio
Hagiwara et al [74] also evaluated extracts of annattofor liver carcinogenicity in rats and found no evidence ofliver tumors even when given to animals at a high dose of200mgkg body weightday compared to an acceptable doseof 00 to 0065mgkgday thus indicating that the dangerof a hepatocarcinogenic effect in humans may be absent ornegligible
A toxicity test was performedwith extracts obtained fromboth plant seeds and shoots and no significant effect wasobserved The experiments were performed in the UnitedStates using mice as the animal model and it was found thatthe LD50 was greater than 700mgkg [92]
9 Correlation between the BiologicalActivities Phytochemistry and theTraditional Uses of Bixa orellana
Table 1 shows that many of the traditional uses of Bixaorellana are the same in several countries of South andCentral America which suggests its effectiveness as a ther-apeutic agent Extracts of Bixa orellana showed biologicalactivities such as antioxidant hypotensive molluscicideand antimalarial against A549 cells for carcinoma of thelung allergy hypoglycemic antifungal antioxidant insectrepellent antigonococcal and antivenom serum and some ofthem are in accordance with the traditional use for examplein Brazil it is used to extract the seeds with purpose repellentinsecticide and antimalaria and scientific studies in the samecountrywith the Lutzomyia longipalpis insect repellent action
and prove a study in Cuba proved the pharmacological actionfor antimalarial activity when tested against Plasmodiumberghei Some of them are in accordance with the traditionaluse for example seed extracts have been used in Brazil andCuba as insect repellent and antimalarial Antioxidant andinsect repellent activities can be attributed to the carotenoidsand the essential and fixed oils respectively
Despite the previous reports about the presence of com-ponents with anti-inflammatory properties such as salicylicacid lutein polyphenols and tannins this activity has not yetbeen proven for Bixa orellana extracts Similarly the plantrsquosessential and fixed oils have shown antibacterial propertiesalthough this activity has not been proven too
In general the data obtained in this review do not allowcorrelations between the biologic activities tested in vitro or invivo with the compounds identified in this species Howevertaking into account the related activities such as the antipara-sitic effect and the lack of mutagenic and cytotoxicity activityit is possible to consider Bixa orellana as a potential source forthe development of phytopharmaceutical products
In conclusion the studies discussed in this review repre-sent a rich database around the Bixa orellana activities andits potential uses which evokes the feasibility of phytophar-maceuticals to treat some diseases whenever an antioxidanthypotensor or hypoglycemiant activity is necessary
Although the commercial exploitation of this species iswell established there are very few studies on its pharma-cological effects Considering the need for developing a safeand effective product more studies should be performed inorder to confirm other biological activities supported by thepopular uses of Bixa orellana
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors are grateful to CNPqPRONEXFAPESQ andCAPES for financial support and to the NAPRALERTDatabase of the University of Illinois USA for the literatureon Bixa orellana A Leyva helped in editing the Englishlanguage of the paper
References
[1] M B Perecin O A Bovi and N B Maia ldquoPesquisa complantas aromaticas medicinais corantes o papel do InstitutoAgronomicordquo O Agronomico vol 54 pp 21ndash24 2002
[2] M E A Elias G Schroth J L V Macedo M S S Motaand S A DrsquoAngelo ldquoMineral nutrition growth and yields ofannatto trees (Bixa orellana) in agroforestry on an AmazonianFerralsolrdquo Experimental Agriculture vol 38 no 3 pp 277ndash2892002
[3] A R R Bastos J G Carvalho R P Assis and A B C FilholdquoMarcha de absorcao de nutrientes em urucum ( Bixa orellanaL) tipo cultivado piave vermelha em fase de viveirordquoCerne vol5 pp 76ndash85 1999
The Scientific World Journal 9
[4] E PThomasM Colvin S B Rosen C Zuccarini and S PetzerldquoHIV prevalence study and costing analysis undertaken for thedevelopment of an HIVAIDS workplace strategy for buffalocity municipalityrdquo Tech Rep Medical Research Council Buf-falo NY USA 2005
[5] C F Franco ldquoO Agronegocio do urucum na regiao Nordesterdquo 1Reuniao Nacional da Cadeia Produtiva de Urucum CD-Rom2007
[6] A Giorgi P De Marinis G Granelli L M Chiesa and SPanseri ldquoSecondary metabolite profile antioxidant capacityand mosquito repellent activity of Bixa orellana from BrazilianAmazon regionrdquo Journal of Chemistry vol 2013 Article ID409826 10 pages 2013
[7] J S Silva M D Moura R A G Oliveira M F F Dinizand J M Barbosa-Filho ldquoNatural product inhibitors of ovarianneoplasiardquo Phytomedicine vol 10 no 2-3 pp 221ndash232 2003
[8] F C F Sousa C T V Melo C O M Cito et al ldquoPlantasmedicinais e seus constituintes bioativos uma revisao dabioatividade e potenciais benefıcios nos disturbios da ansiedadeem modelos animaisrdquo Revista Brasileira de Farmacognosia vol18 pp 642ndash654 2008
[9] L J Quintans Jr J R G S Almeida J T Lima et al ldquoPlantswith anticonvulsant propertiesmdasha reviewrdquo Revista Brasileira deFarmacognosia vol 18 pp 798ndash819 2008
[10] HD S Falcao J A Leite JM Barbosa-Filho et al ldquoGastric andduodenal antiulcer activity of alkaloids a reviewrdquoMolecules vol13 no 12 pp 3198ndash3223 2008
[11] H S Falcao I R Mariath M F F M Diniz L M Batista andJ M Barbosa-Filho ldquoPlants of the American continent withantiulcer activityrdquo Phytomedicine vol 15 no 1-2 pp 132ndash1462008
[12] I R Mariath H D S Falcao J M Barbosa-Filho et al ldquoPlantsof the American continent with antimalarial activityrdquo RevistaBrasileira de Farmacognosia vol 19 no 1 pp 158ndash192 2009
[13] J E R Hon P M Soares C L Melo et al ldquoAtividadefarmacologica da monocrotalina isolada de plantas do generoCrotalariardquo Revista Brasileira de Farmacognosia vol 20 pp453ndash458 2010
[14] R N Almeida D S Navarro and J M Barbosa-Filho ldquoPlantswith central analgesic activityrdquo Phytomedicine vol 8 no 4 pp310ndash322 2001
[15] N Z T Jesus H S Falcao I F Gomes et al ldquoTanninspeptic ulcers and related mechanismsrdquo International Journal ofMolecular Sciences vol 13 no 3 pp 3203ndash3228 2012
[16] L G Rocha J R G S Almeida R O Macedo and J MBarbosa-Filho ldquoA review of natural products with antileishma-nial activityrdquo Phytomedicine vol 12 no 6-7 pp 514ndash535 2005
[17] G R M Lima C A Montenegro C L F Almeida PF Athayde-Filho J M Barbosa-Filho and L M BatistaldquoDatabase survey of anti-inflammatory plants in South Amer-ica a reviewrdquo International Journal ofMolecular Sciences vol 12no 4 pp 2692ndash2749 2011
[18] K S De Lira Mota G E N Dias M E F Pinto et alldquoFlavonoids with gastroprotective activityrdquo Molecules vol 14no 3 pp 979ndash1012 2009
[19] A L Souto J F Tavares M S da Silva M F F M de Diniz P Fde Athayde-Filho and J M Barbosa Filho ldquoAnti-inflammatoryactivity of alkaloids an update from 2000 to 2010rdquo Moleculesvol 16 no 10 pp 8515ndash8534 2011
[20] F L Silva D C H Fischer J F Tavares M S Silva P Fde Athayde-Filho and J M Barbosa-Filho ldquoCompilation of
secondary metabolites from Bidens pilosa LrdquoMolecules vol 16no 2 pp 1070ndash1102 2011
[21] J R Filho H de Sousa Falcao L M Batista J M B Filho andM R Piuvezam ldquoEffects of plant extracts on HIV-1 proteaserdquoCurrent HIV Research vol 8 no 7 pp 531ndash544 2010
[22] JM Barbosa-Filho A A Alencar X P Nunes et al ldquoSources ofalpha- beta- gamma- delta- and epsilon-carotenes a twentiethcentury reviewrdquo Revista Brasileirta de Farmacogn vol 18 no 1pp 135ndash154 2008
[23] S N S Silva C L F Amaral and T N H Reboucas ldquoAdoptionof conservation practices on farm and selection of varieties byproducers of annatto in the city of Vitoria da Conquista-BArdquoRevista Brasileira de Agroecologica vol 5 pp 106ndash113 2010
[24] A L Bandoni M E Mendiondo R V D Rondina and J DCoussio ldquoSurvey of Argentine medicinal plants I Folklore andphytochemical screeningrdquo Lloydia vol 35 no 1ndash4 pp 69ndash801972
[25] G H Garcia R Campos R A de Torres et al ldquoAntiherpeticactivity of some Argentine medicinal plantsrdquo Fitoterapia vol61 no 6 pp 542ndash546 1990
[26] M G L Brandao T S M Grandi E M M Rocha D RSawyer and A U Krettli ldquoSurvey of medicinal plants used asantimalarials in the Amazonrdquo Journal of Ethnopharmacologyvol 36 no 2 pp 175ndash182 1992
[27] M P Correa Dicionario das Plantas Uteis do Brasil e dasExoticas Cultivadas vol 4 Ministerio da AgriculturaIBDF Riode Janeiro Brasil 1978
[28] G S Hirschmann and A R de Arias ldquoA survey of medicinalplants of minas gerais Brazilrdquo Journal of Ethnopharmacologyvol 29 no 2 pp 159ndash172 1990
[29] R Otero R Fonnegra S L Jimenez et al ldquoSnakebites andethnobotany in the northwest region of Colombia Part Itraditional use of plantsrdquo Journal of Ethnopharmacology vol 71no 3 pp 493ndash504 2000
[30] H Garcia-Barriga Flora Medicinal de Colombia vol 2 Univer-sidad Nacional Bogota Colombia 1975
[31] J T Roig y Mesa Plantas Medicinales Aromaticas o Venenosasde Cuba Ministerio de Agricultura Havana Cuba 1945
[32] A Caceres H Menendez E Mendez et al ldquoAntigonorrhoealactivity of plants used inGuatemala for the treatment of sexuallytransmitted diseasesrdquo Journal of Ethnopharmacology vol 48no 2 pp 85ndash88 1995
[33] J A Duke and R V Martinez Amazonian EthnobotanicalDictionary CRC Press Boca Raton Fla USA 1994
[34] V R Ramirez L J Mostacero A E Garcia et al VegetalesEmpleados enMedicina Tradicional Norperuana Banco Agrariodel Peru Universidad Nacional de Trujillo Trujillo Peru 1988
[35] R Villar J M Calleja C Morales and A Caceres ldquoScreeningof 17 Guatemalan medicinal plants for platelet antiaggregantactivityrdquo Phytotherapy Research vol 11 pp 441ndash445 1997
[36] L M Giron V Freire A Alonzo and A Caceres ldquoEthnob-otanical survey of the medicinal flora used by the Caribs ofGuatemalardquo Journal of Ethnopharmacology vol 34 no 2-3 pp173ndash187 1991
[37] D L Lentz ldquoMedicinal and other economic plants of the PayaofHondurasrdquo Economic Botany vol 47 no 4 pp 358ndash370 1993
[38] D L Lentz A M Clark C D Hufford et al ldquoAntimi-crobial properties of Honduran medicinal plantsrdquo Journal ofEthnopharmacology vol 63 no 3 pp 253ndash263 1998
[39] E Y Morrison and M E West ldquoThe effect of Bixa orellana(Annatto) on blood sugar levels in the anaesthetized dogrdquoWestIndian Medical Journal vol 34 no 1 pp 38ndash42 1985
10 The Scientific World Journal
[40] F G Coe and G J Anderson ldquoScreening of medicinal plantsused by the Garıfuna of eastern Nicaragua for bioactive com-poundsrdquo Journal of Ethnopharmacology vol 53 no 1 pp 29ndash501996
[41] B Barrett ldquoMedicinal plants of Nicaraguarsquos Atlantic CoastrdquoEconomic Botany vol 48 no 1 pp 8ndash20 1994
[42] G Schmeda-Hirschmann and A R de Arias ldquoA screeningmethod for natural products on triatomine bugsrdquo PhytotherapyResearch vol 6 no 2 pp 68ndash73 1992
[43] G E Simpson ldquoFolk medicine in Trinidadrdquo The Journal ofAmerican Folklore vol 75 no 298 pp 326ndash340 1962
[44] D Mahabir and M C Gulliford ldquoUse of medicinal plants fordiabetes in Trinidad and Tobagordquo Revista Panamericana deSalud Publica vol 1 no 3 pp 174ndash179 1997
[45] E S Ayensu ldquoMedicinal plants of theWest IndiesrdquoUnpublishedManuscript 1978
[46] A Z Mercadante A Steck D Rodriguez-Amaya H Pfanderand G Britton ldquoIsolation of methyl 91015840Z-APO-61015840-lycopenoatefrom Bixa Orellanardquo Phytochemistry vol 41 no 4 pp 1201ndash1203 1996
[47] E Angelucci H K Arima E A Kumagai and I AnnattoldquoPreliminary data of the chemical compositionrdquo Coletanea doInstituto de Tecnologia de Alimentos vol 11 pp 89ndash96 1980
[48] A S L Tirimanna ldquoStudy of the carotenoid pigments of Bixaorellana L Seeds by thin layer chromatographyrdquo MikrochimicaActa vol 76 no 1-2 pp 11ndash16 1981
[49] J M Barbosa-Filho R N Silva-Filho B F Lira et al ldquoTeor debixina em quatro variedades de Bixa orellana L cultivadas naParaıbardquo Revista Brasileira de Farmacognosia vol 7-8 pp 41ndash47 1998
[50] A Z Mercadante A Steck and H Pfander ldquoIsolation andstructure elucidation of minor carotenoids from annatto (Bixaorellana L) seedsrdquo Phytochemistry vol 46 no 8 pp 1379ndash13831997
[51] C Prentice-Hernandez and O Rusig ldquoAnnatto (Bixa orellanaL) extract obtained using ethyl alcohol as a solventrdquo Arquivosde Biologia e Tecnologia vol 35 pp 63ndash74 1992
[52] A Z Mercadante ldquoComposition of carotenoids from annattordquoACS Symposium Series vol 775 pp 92ndash101 2001
[53] M J Scotter L A Wilson G P Appleton and L CastleldquoAnalysis of Annatto (Bixa orellana) Food Coloring Formula-tions 1 Determination of Coloring Components and ColoredThermal Degradation Products by High-Performance LiquidChromatography with Photodiode Array Detectionrdquo Journal ofAgricultural and Food Chemistry vol 46 no 3 pp 1031ndash10381998
[54] A J Degnan J H von Elbe and R W Hartel ldquoExtraction ofannatto seed pigment by supercritical carbon dioxiderdquo Journalof Food Science vol 56 pp 1655ndash1659 1991
[55] A ZMercadante A Steck andH Pfander ldquoIsolation and iden-tification of new apocarotenoids from annatto (Bixa orellana)seedsrdquo Journal of Agricultural and Food Chemistry vol 45 no4 pp 1050ndash1054 1997
[56] S G Anderson M G Nair A Chandra and E MorrisonldquoSupercritical fluid carbon dioxide extraction of annatto seedsand quantification of trans-bixin by high pressure liquid chro-matographyrdquo Phytochemical Analysis vol 8 pp 247ndash249 1997
[57] J M Barbosa-Filho Bixa orellana Retrospectiva de usos pop-ulares atividades biologicas fitoquımica e emprego na fito-cosmetica no continente americano Simposio Brasileiro doUrucummdashSIMBRAU Joao Pessoa Brazil 2006
[58] J Revilla Plantas da Amazonia Oportunidades Economicas eSustentaveis Manaus Programa de Desenvolvimento Empre-sarial e Tecnologico 2nd edition 2001
[59] F Oliveira G Akisue and M K Akisue FarmacognosiaAtheneu Sao Paulo Brazil 1996
[60] J Alonso Tratado de Fitofarmacos y Nutraceuticos CorpusRosario Argentina 2004
[61] C O Franco E G Fabri M Barreiro Neto M H Manfiolli MN C Harder and N C Rucker Urucum Sistema de Producaopara o Brasil Emepa-Pb Apta Joao Pessoa Brazil 2008
[62] P A Venugopalan G A Giridhar and A G RavishankarldquoFood Ethanobotanical and diversified applications of Bixaorellana L a scope for its improvement through biotechnolog-ical mediationrdquo Indian Journal of Fundamental and Applied LifeSciences vol 1 pp 9ndash31 2011
[63] L Taylor Herbal Secrets of the Rainforest Sage Press RocklinCalif USA 2nd edition 2002
[64] J S Oliveira Caracterizacao Extracao e Purificacao por Cro-matografia de Compostos de Urucum (Bixa orellana L) [tesisdoctoral en Ingenierıa Quımic] Universidade Federal de SantaCatarina Florianopolis Brazil 2005
[65] A Z Mercadante A Steck and H Pfander ldquoThree minorcarotenoids from annatto (Bixa orellana) seedsrdquo Phytochem-istry vol 52 no 1 pp 135ndash139 1999
[66] V Galindo-Cuspinera M B Lubran and S A Rankin ldquoCom-parison of volatile compounds in water- and oil-soluble annatto(Bixa orellana L) extractsrdquo Journal of Agricultural and FoodChemistry vol 50 no 7 pp 2010ndash2015 2002
[67] R O Alves de Lima L Azevedo L R Ribeiro and D M FSalvadori ldquoStudy on the mutagenicity and antimutagenicity ofa natural food colour (annatto) in mouse bone marrow cellsrdquoFood and Chemical Toxicology vol 41 no 2 pp 189ndash192 2003
[68] L R P Lima T T Oliveira T J Nagem et al ldquoBixina norbixinae quercetina e seus efeitos no metabolismo lipıdico de coelhosrdquoBrazilian Journal of Veterinary Research andAnimal Science vol38 pp 196ndash200 2001
[69] J D Fontana S V Mendes D S Persike L F Peracetta andM Passos ldquoCarotenoides cores atraentes e acao biologicardquoBiotecnologia Ciencia amp Desenvolvimento vol 2 p 13 2000
[70] C A Penna M Radice G O Gutkind et al ldquoAntibacterial andantifungal activities of some Argentinean plantsrdquo Fitoterapiavol 65 no 2 pp 172ndash174 1994
[71] A M Broussalis G E Ferraro V S Martino R Pinzon J DCoussio and J C Alvarez ldquoArgentine plants as potential sourceof insecticidal compoundsrdquo Journal of Ethnopharmacology vol67 no 2 pp 219ndash223 1999
[72] A Rojas de Arias G Schmeda-Hirschmann and A FalcaoldquoFeeding deterrency and insecticidal effects of plant extracts onLutzomyia longipalpisrdquo Phytotherapy Research vol 6 no 2 pp64ndash67 1992
[73] M S Pinheiro and M Z Rouquayrol ldquoMolluscicidal activityof plants from Northeast Brazilrdquo Revista Brasileira de PesquisasMedicas e Biologicas vol 7 pp 389ndash394 1974
[74] A Hagiwara N Imai T Ichihara et al ldquoA thirteen-week oraltoxicity study of annatto extract (norbixin) a natural food colorextracted from the seed coat of annatto (Bixa orellana L) inSprague-Dawley ratsrdquoFood andChemical Toxicology vol 41 no8 pp 1157ndash1164 2003
[75] C R Almeida R B Silva M J Marques and J K ChavascoldquoEvaluation of antiparasitic activity of hydroethanolic extractsfrom root stem and leaf of Bixa orellana L on Leishmania
The Scientific World Journal 11
amazonensis samplesrdquo Revista da Universidade Vale do RioVerde vol 10 no 2 pp 384ndash391 2012
[76] M V Lopes V C Desoti A D O Caleare T Ueda-NakamuraS O Silva and C V Nakamura ldquoMitochondria superoxideanion production contributes to geranylgeraniol-induced deathin leishmania amazonensisrdquo Evidence-Based Complementaryand Alternative Medicine vol 2012 Article ID 298320 9 pages2012
[77] J M Ferreira D F Sousa M B Dantas et al ldquoEffects of BixaorellanaL seeds onhyperlipidemiardquoPhytotherapyResearch vol27 no 1 pp 144ndash147 2013
[78] P S BenoitHH S FongGH Svoboda andN R FarnsworthldquoBiological and phytochemical evaluation of plants XIV Anti-inflammatory evaluation of 163 species of plantsrdquo Lloydia vol39 no 2-3 pp 160ndash171 1976
[79] D Carabajal A Casaco L Arruzazabala R Gonzalez andV Fuentes ldquoPharmacological screening of plant decoctionscommonly used in Cuban folk medicinerdquo Journal of Ethnophar-macology vol 33 no 1-2 pp 21ndash24 1991
[80] A F C Valdes J M Martınez D A Rodrıguez R S Lizamaand Y G Gaiten ldquoActividad antimalarica de un extractohidroalcoholico de Bixa orellanaLrdquo Revista Cubana de Medic-ina Tropical vol 63 pp 181ndash185 2011
[81] A D Garcıa H R Sanchez and R S Lizama ldquoCitotoxicidadde extractos de plantas medicinales sobre la lınea celularde carcinoma de pulmon humano A549rdquo Revista Cubana deFarmacia vol 45 pp 101ndash108 2011
[82] B Freixa R Vila L Vargas N Lozano T Adzet and SCanigueral ldquoScreening for antifungal activity of nineteen LatinAmerican plantsrdquo Phytotherapy Research vol 12 no 6 pp 427ndash430 1998
[83] A Caceres B Lopez S Gonzalez I Berger I Tada and JMaki ldquoPlants used in Guatemala for the treatment of pro-tozoal infections I Screening of activity to bacteria fungiand American trypanosomes of 13 native plantsrdquo Journal ofEthnopharmacology vol 62 no 3 pp 195ndash202 1998
[84] A Caceres O Cano B Samayoa and L Aguilar ldquoPlants usedin Guatemala for the treatment of gastrointestinal disorders1 Screening of 84 plants against enterobacteriardquo Journal ofEthnopharmacology vol 30 no 1 pp 55ndash73 1990
[85] A S Matsui S Hoskin M Kashiwagi et al ldquoA survey ofnatural products from Hawaii and other areas of the Pacificfor an antifertility effect in micerdquo Internationale Zeitschrift furKlinische PharmakologieTherapie und Toxikologie vol 5 no 1pp 65ndash69 1971
[86] M Abayomi A S Adebayo D Bennett R Porter and JS Campbell ldquoIn vitro antioxidant activity of Bixa orellana(Annatto) seed extractrdquo Journal of Applied PharmaceuticalScience vol 4 no 2 pp 101ndash106 2014
[87] NW Dunham and K R Allard ldquoA preliminary pharmacologicinvestigation of the roots of Bixa orellanardquo Journal of theAmerican Pharmacist Associantion vol 49 pp 218ndash219 1960
[88] F RMedina andRWoodbury ldquoTerrestrial plantsmolluscicidalto lymnaeid hosts of Fasciliasis hepatica in Puerto Ricordquo Journalof Agricultura of the University of Puerto Rico vol 63 pp 366ndash376 1979
[89] B Weniger Y Jiang A Oulad-Ali L Italiano J P Beck and RAnton ldquoBiological effects of bixin and Bixa orellana extracts onlymphoid cells in culturerdquo Planta Medica vol 59 no 7 articleA680 1993
[90] CM Chariandy C E Seaforth R H Phelps G V Pollard andB P S Khambay ldquoScreening of medicinal plants from Trinidad
and Tobago for antimicrobial and insecticidal propertiesrdquoJournal of Ethnopharmacology vol 64 no 3 pp 265ndash270 1999
[91] F J R Paumgartten R R Carvalho I B Araujo et alldquoEvaluation of the developmental toxicity of annatto in the ratrdquoFood and Chemical Toxicology vol 40 no 11 pp 1595ndash16012002
[92] C F Spencer F R Koniuszy E F Rogers et al ldquoSurvey of plantsfor antimalarial activityrdquo Lloydia vol 10 no 3 pp 145ndash174 1947
[93] H Mikkelsen J C Larsen and F Tarding ldquoHypersensitivityreactions to food colours with special reference to the naturalcolour annatto extract (butter colour)rdquo Toxicological Aspects ofFood Safety vol 1 pp 141ndash143 1978
Submit your manuscripts athttpwwwhindawicom
PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom
Volume 2014
ToxinsJournal of
VaccinesJournal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
AntibioticsInternational Journal of
ToxicologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Drug DeliveryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in Pharmacological Sciences
Tropical MedicineJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
AddictionJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Autoimmune Diseases
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Anesthesiology Research and Practice
ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Pharmaceutics
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
The Scientific World Journal 9
[4] E PThomasM Colvin S B Rosen C Zuccarini and S PetzerldquoHIV prevalence study and costing analysis undertaken for thedevelopment of an HIVAIDS workplace strategy for buffalocity municipalityrdquo Tech Rep Medical Research Council Buf-falo NY USA 2005
[5] C F Franco ldquoO Agronegocio do urucum na regiao Nordesterdquo 1Reuniao Nacional da Cadeia Produtiva de Urucum CD-Rom2007
[6] A Giorgi P De Marinis G Granelli L M Chiesa and SPanseri ldquoSecondary metabolite profile antioxidant capacityand mosquito repellent activity of Bixa orellana from BrazilianAmazon regionrdquo Journal of Chemistry vol 2013 Article ID409826 10 pages 2013
[7] J S Silva M D Moura R A G Oliveira M F F Dinizand J M Barbosa-Filho ldquoNatural product inhibitors of ovarianneoplasiardquo Phytomedicine vol 10 no 2-3 pp 221ndash232 2003
[8] F C F Sousa C T V Melo C O M Cito et al ldquoPlantasmedicinais e seus constituintes bioativos uma revisao dabioatividade e potenciais benefıcios nos disturbios da ansiedadeem modelos animaisrdquo Revista Brasileira de Farmacognosia vol18 pp 642ndash654 2008
[9] L J Quintans Jr J R G S Almeida J T Lima et al ldquoPlantswith anticonvulsant propertiesmdasha reviewrdquo Revista Brasileira deFarmacognosia vol 18 pp 798ndash819 2008
[10] HD S Falcao J A Leite JM Barbosa-Filho et al ldquoGastric andduodenal antiulcer activity of alkaloids a reviewrdquoMolecules vol13 no 12 pp 3198ndash3223 2008
[11] H S Falcao I R Mariath M F F M Diniz L M Batista andJ M Barbosa-Filho ldquoPlants of the American continent withantiulcer activityrdquo Phytomedicine vol 15 no 1-2 pp 132ndash1462008
[12] I R Mariath H D S Falcao J M Barbosa-Filho et al ldquoPlantsof the American continent with antimalarial activityrdquo RevistaBrasileira de Farmacognosia vol 19 no 1 pp 158ndash192 2009
[13] J E R Hon P M Soares C L Melo et al ldquoAtividadefarmacologica da monocrotalina isolada de plantas do generoCrotalariardquo Revista Brasileira de Farmacognosia vol 20 pp453ndash458 2010
[14] R N Almeida D S Navarro and J M Barbosa-Filho ldquoPlantswith central analgesic activityrdquo Phytomedicine vol 8 no 4 pp310ndash322 2001
[15] N Z T Jesus H S Falcao I F Gomes et al ldquoTanninspeptic ulcers and related mechanismsrdquo International Journal ofMolecular Sciences vol 13 no 3 pp 3203ndash3228 2012
[16] L G Rocha J R G S Almeida R O Macedo and J MBarbosa-Filho ldquoA review of natural products with antileishma-nial activityrdquo Phytomedicine vol 12 no 6-7 pp 514ndash535 2005
[17] G R M Lima C A Montenegro C L F Almeida PF Athayde-Filho J M Barbosa-Filho and L M BatistaldquoDatabase survey of anti-inflammatory plants in South Amer-ica a reviewrdquo International Journal ofMolecular Sciences vol 12no 4 pp 2692ndash2749 2011
[18] K S De Lira Mota G E N Dias M E F Pinto et alldquoFlavonoids with gastroprotective activityrdquo Molecules vol 14no 3 pp 979ndash1012 2009
[19] A L Souto J F Tavares M S da Silva M F F M de Diniz P Fde Athayde-Filho and J M Barbosa Filho ldquoAnti-inflammatoryactivity of alkaloids an update from 2000 to 2010rdquo Moleculesvol 16 no 10 pp 8515ndash8534 2011
[20] F L Silva D C H Fischer J F Tavares M S Silva P Fde Athayde-Filho and J M Barbosa-Filho ldquoCompilation of
secondary metabolites from Bidens pilosa LrdquoMolecules vol 16no 2 pp 1070ndash1102 2011
[21] J R Filho H de Sousa Falcao L M Batista J M B Filho andM R Piuvezam ldquoEffects of plant extracts on HIV-1 proteaserdquoCurrent HIV Research vol 8 no 7 pp 531ndash544 2010
[22] JM Barbosa-Filho A A Alencar X P Nunes et al ldquoSources ofalpha- beta- gamma- delta- and epsilon-carotenes a twentiethcentury reviewrdquo Revista Brasileirta de Farmacogn vol 18 no 1pp 135ndash154 2008
[23] S N S Silva C L F Amaral and T N H Reboucas ldquoAdoptionof conservation practices on farm and selection of varieties byproducers of annatto in the city of Vitoria da Conquista-BArdquoRevista Brasileira de Agroecologica vol 5 pp 106ndash113 2010
[24] A L Bandoni M E Mendiondo R V D Rondina and J DCoussio ldquoSurvey of Argentine medicinal plants I Folklore andphytochemical screeningrdquo Lloydia vol 35 no 1ndash4 pp 69ndash801972
[25] G H Garcia R Campos R A de Torres et al ldquoAntiherpeticactivity of some Argentine medicinal plantsrdquo Fitoterapia vol61 no 6 pp 542ndash546 1990
[26] M G L Brandao T S M Grandi E M M Rocha D RSawyer and A U Krettli ldquoSurvey of medicinal plants used asantimalarials in the Amazonrdquo Journal of Ethnopharmacologyvol 36 no 2 pp 175ndash182 1992
[27] M P Correa Dicionario das Plantas Uteis do Brasil e dasExoticas Cultivadas vol 4 Ministerio da AgriculturaIBDF Riode Janeiro Brasil 1978
[28] G S Hirschmann and A R de Arias ldquoA survey of medicinalplants of minas gerais Brazilrdquo Journal of Ethnopharmacologyvol 29 no 2 pp 159ndash172 1990
[29] R Otero R Fonnegra S L Jimenez et al ldquoSnakebites andethnobotany in the northwest region of Colombia Part Itraditional use of plantsrdquo Journal of Ethnopharmacology vol 71no 3 pp 493ndash504 2000
[30] H Garcia-Barriga Flora Medicinal de Colombia vol 2 Univer-sidad Nacional Bogota Colombia 1975
[31] J T Roig y Mesa Plantas Medicinales Aromaticas o Venenosasde Cuba Ministerio de Agricultura Havana Cuba 1945
[32] A Caceres H Menendez E Mendez et al ldquoAntigonorrhoealactivity of plants used inGuatemala for the treatment of sexuallytransmitted diseasesrdquo Journal of Ethnopharmacology vol 48no 2 pp 85ndash88 1995
[33] J A Duke and R V Martinez Amazonian EthnobotanicalDictionary CRC Press Boca Raton Fla USA 1994
[34] V R Ramirez L J Mostacero A E Garcia et al VegetalesEmpleados enMedicina Tradicional Norperuana Banco Agrariodel Peru Universidad Nacional de Trujillo Trujillo Peru 1988
[35] R Villar J M Calleja C Morales and A Caceres ldquoScreeningof 17 Guatemalan medicinal plants for platelet antiaggregantactivityrdquo Phytotherapy Research vol 11 pp 441ndash445 1997
[36] L M Giron V Freire A Alonzo and A Caceres ldquoEthnob-otanical survey of the medicinal flora used by the Caribs ofGuatemalardquo Journal of Ethnopharmacology vol 34 no 2-3 pp173ndash187 1991
[37] D L Lentz ldquoMedicinal and other economic plants of the PayaofHondurasrdquo Economic Botany vol 47 no 4 pp 358ndash370 1993
[38] D L Lentz A M Clark C D Hufford et al ldquoAntimi-crobial properties of Honduran medicinal plantsrdquo Journal ofEthnopharmacology vol 63 no 3 pp 253ndash263 1998
[39] E Y Morrison and M E West ldquoThe effect of Bixa orellana(Annatto) on blood sugar levels in the anaesthetized dogrdquoWestIndian Medical Journal vol 34 no 1 pp 38ndash42 1985
10 The Scientific World Journal
[40] F G Coe and G J Anderson ldquoScreening of medicinal plantsused by the Garıfuna of eastern Nicaragua for bioactive com-poundsrdquo Journal of Ethnopharmacology vol 53 no 1 pp 29ndash501996
[41] B Barrett ldquoMedicinal plants of Nicaraguarsquos Atlantic CoastrdquoEconomic Botany vol 48 no 1 pp 8ndash20 1994
[42] G Schmeda-Hirschmann and A R de Arias ldquoA screeningmethod for natural products on triatomine bugsrdquo PhytotherapyResearch vol 6 no 2 pp 68ndash73 1992
[43] G E Simpson ldquoFolk medicine in Trinidadrdquo The Journal ofAmerican Folklore vol 75 no 298 pp 326ndash340 1962
[44] D Mahabir and M C Gulliford ldquoUse of medicinal plants fordiabetes in Trinidad and Tobagordquo Revista Panamericana deSalud Publica vol 1 no 3 pp 174ndash179 1997
[45] E S Ayensu ldquoMedicinal plants of theWest IndiesrdquoUnpublishedManuscript 1978
[46] A Z Mercadante A Steck D Rodriguez-Amaya H Pfanderand G Britton ldquoIsolation of methyl 91015840Z-APO-61015840-lycopenoatefrom Bixa Orellanardquo Phytochemistry vol 41 no 4 pp 1201ndash1203 1996
[47] E Angelucci H K Arima E A Kumagai and I AnnattoldquoPreliminary data of the chemical compositionrdquo Coletanea doInstituto de Tecnologia de Alimentos vol 11 pp 89ndash96 1980
[48] A S L Tirimanna ldquoStudy of the carotenoid pigments of Bixaorellana L Seeds by thin layer chromatographyrdquo MikrochimicaActa vol 76 no 1-2 pp 11ndash16 1981
[49] J M Barbosa-Filho R N Silva-Filho B F Lira et al ldquoTeor debixina em quatro variedades de Bixa orellana L cultivadas naParaıbardquo Revista Brasileira de Farmacognosia vol 7-8 pp 41ndash47 1998
[50] A Z Mercadante A Steck and H Pfander ldquoIsolation andstructure elucidation of minor carotenoids from annatto (Bixaorellana L) seedsrdquo Phytochemistry vol 46 no 8 pp 1379ndash13831997
[51] C Prentice-Hernandez and O Rusig ldquoAnnatto (Bixa orellanaL) extract obtained using ethyl alcohol as a solventrdquo Arquivosde Biologia e Tecnologia vol 35 pp 63ndash74 1992
[52] A Z Mercadante ldquoComposition of carotenoids from annattordquoACS Symposium Series vol 775 pp 92ndash101 2001
[53] M J Scotter L A Wilson G P Appleton and L CastleldquoAnalysis of Annatto (Bixa orellana) Food Coloring Formula-tions 1 Determination of Coloring Components and ColoredThermal Degradation Products by High-Performance LiquidChromatography with Photodiode Array Detectionrdquo Journal ofAgricultural and Food Chemistry vol 46 no 3 pp 1031ndash10381998
[54] A J Degnan J H von Elbe and R W Hartel ldquoExtraction ofannatto seed pigment by supercritical carbon dioxiderdquo Journalof Food Science vol 56 pp 1655ndash1659 1991
[55] A ZMercadante A Steck andH Pfander ldquoIsolation and iden-tification of new apocarotenoids from annatto (Bixa orellana)seedsrdquo Journal of Agricultural and Food Chemistry vol 45 no4 pp 1050ndash1054 1997
[56] S G Anderson M G Nair A Chandra and E MorrisonldquoSupercritical fluid carbon dioxide extraction of annatto seedsand quantification of trans-bixin by high pressure liquid chro-matographyrdquo Phytochemical Analysis vol 8 pp 247ndash249 1997
[57] J M Barbosa-Filho Bixa orellana Retrospectiva de usos pop-ulares atividades biologicas fitoquımica e emprego na fito-cosmetica no continente americano Simposio Brasileiro doUrucummdashSIMBRAU Joao Pessoa Brazil 2006
[58] J Revilla Plantas da Amazonia Oportunidades Economicas eSustentaveis Manaus Programa de Desenvolvimento Empre-sarial e Tecnologico 2nd edition 2001
[59] F Oliveira G Akisue and M K Akisue FarmacognosiaAtheneu Sao Paulo Brazil 1996
[60] J Alonso Tratado de Fitofarmacos y Nutraceuticos CorpusRosario Argentina 2004
[61] C O Franco E G Fabri M Barreiro Neto M H Manfiolli MN C Harder and N C Rucker Urucum Sistema de Producaopara o Brasil Emepa-Pb Apta Joao Pessoa Brazil 2008
[62] P A Venugopalan G A Giridhar and A G RavishankarldquoFood Ethanobotanical and diversified applications of Bixaorellana L a scope for its improvement through biotechnolog-ical mediationrdquo Indian Journal of Fundamental and Applied LifeSciences vol 1 pp 9ndash31 2011
[63] L Taylor Herbal Secrets of the Rainforest Sage Press RocklinCalif USA 2nd edition 2002
[64] J S Oliveira Caracterizacao Extracao e Purificacao por Cro-matografia de Compostos de Urucum (Bixa orellana L) [tesisdoctoral en Ingenierıa Quımic] Universidade Federal de SantaCatarina Florianopolis Brazil 2005
[65] A Z Mercadante A Steck and H Pfander ldquoThree minorcarotenoids from annatto (Bixa orellana) seedsrdquo Phytochem-istry vol 52 no 1 pp 135ndash139 1999
[66] V Galindo-Cuspinera M B Lubran and S A Rankin ldquoCom-parison of volatile compounds in water- and oil-soluble annatto(Bixa orellana L) extractsrdquo Journal of Agricultural and FoodChemistry vol 50 no 7 pp 2010ndash2015 2002
[67] R O Alves de Lima L Azevedo L R Ribeiro and D M FSalvadori ldquoStudy on the mutagenicity and antimutagenicity ofa natural food colour (annatto) in mouse bone marrow cellsrdquoFood and Chemical Toxicology vol 41 no 2 pp 189ndash192 2003
[68] L R P Lima T T Oliveira T J Nagem et al ldquoBixina norbixinae quercetina e seus efeitos no metabolismo lipıdico de coelhosrdquoBrazilian Journal of Veterinary Research andAnimal Science vol38 pp 196ndash200 2001
[69] J D Fontana S V Mendes D S Persike L F Peracetta andM Passos ldquoCarotenoides cores atraentes e acao biologicardquoBiotecnologia Ciencia amp Desenvolvimento vol 2 p 13 2000
[70] C A Penna M Radice G O Gutkind et al ldquoAntibacterial andantifungal activities of some Argentinean plantsrdquo Fitoterapiavol 65 no 2 pp 172ndash174 1994
[71] A M Broussalis G E Ferraro V S Martino R Pinzon J DCoussio and J C Alvarez ldquoArgentine plants as potential sourceof insecticidal compoundsrdquo Journal of Ethnopharmacology vol67 no 2 pp 219ndash223 1999
[72] A Rojas de Arias G Schmeda-Hirschmann and A FalcaoldquoFeeding deterrency and insecticidal effects of plant extracts onLutzomyia longipalpisrdquo Phytotherapy Research vol 6 no 2 pp64ndash67 1992
[73] M S Pinheiro and M Z Rouquayrol ldquoMolluscicidal activityof plants from Northeast Brazilrdquo Revista Brasileira de PesquisasMedicas e Biologicas vol 7 pp 389ndash394 1974
[74] A Hagiwara N Imai T Ichihara et al ldquoA thirteen-week oraltoxicity study of annatto extract (norbixin) a natural food colorextracted from the seed coat of annatto (Bixa orellana L) inSprague-Dawley ratsrdquoFood andChemical Toxicology vol 41 no8 pp 1157ndash1164 2003
[75] C R Almeida R B Silva M J Marques and J K ChavascoldquoEvaluation of antiparasitic activity of hydroethanolic extractsfrom root stem and leaf of Bixa orellana L on Leishmania
The Scientific World Journal 11
amazonensis samplesrdquo Revista da Universidade Vale do RioVerde vol 10 no 2 pp 384ndash391 2012
[76] M V Lopes V C Desoti A D O Caleare T Ueda-NakamuraS O Silva and C V Nakamura ldquoMitochondria superoxideanion production contributes to geranylgeraniol-induced deathin leishmania amazonensisrdquo Evidence-Based Complementaryand Alternative Medicine vol 2012 Article ID 298320 9 pages2012
[77] J M Ferreira D F Sousa M B Dantas et al ldquoEffects of BixaorellanaL seeds onhyperlipidemiardquoPhytotherapyResearch vol27 no 1 pp 144ndash147 2013
[78] P S BenoitHH S FongGH Svoboda andN R FarnsworthldquoBiological and phytochemical evaluation of plants XIV Anti-inflammatory evaluation of 163 species of plantsrdquo Lloydia vol39 no 2-3 pp 160ndash171 1976
[79] D Carabajal A Casaco L Arruzazabala R Gonzalez andV Fuentes ldquoPharmacological screening of plant decoctionscommonly used in Cuban folk medicinerdquo Journal of Ethnophar-macology vol 33 no 1-2 pp 21ndash24 1991
[80] A F C Valdes J M Martınez D A Rodrıguez R S Lizamaand Y G Gaiten ldquoActividad antimalarica de un extractohidroalcoholico de Bixa orellanaLrdquo Revista Cubana de Medic-ina Tropical vol 63 pp 181ndash185 2011
[81] A D Garcıa H R Sanchez and R S Lizama ldquoCitotoxicidadde extractos de plantas medicinales sobre la lınea celularde carcinoma de pulmon humano A549rdquo Revista Cubana deFarmacia vol 45 pp 101ndash108 2011
[82] B Freixa R Vila L Vargas N Lozano T Adzet and SCanigueral ldquoScreening for antifungal activity of nineteen LatinAmerican plantsrdquo Phytotherapy Research vol 12 no 6 pp 427ndash430 1998
[83] A Caceres B Lopez S Gonzalez I Berger I Tada and JMaki ldquoPlants used in Guatemala for the treatment of pro-tozoal infections I Screening of activity to bacteria fungiand American trypanosomes of 13 native plantsrdquo Journal ofEthnopharmacology vol 62 no 3 pp 195ndash202 1998
[84] A Caceres O Cano B Samayoa and L Aguilar ldquoPlants usedin Guatemala for the treatment of gastrointestinal disorders1 Screening of 84 plants against enterobacteriardquo Journal ofEthnopharmacology vol 30 no 1 pp 55ndash73 1990
[85] A S Matsui S Hoskin M Kashiwagi et al ldquoA survey ofnatural products from Hawaii and other areas of the Pacificfor an antifertility effect in micerdquo Internationale Zeitschrift furKlinische PharmakologieTherapie und Toxikologie vol 5 no 1pp 65ndash69 1971
[86] M Abayomi A S Adebayo D Bennett R Porter and JS Campbell ldquoIn vitro antioxidant activity of Bixa orellana(Annatto) seed extractrdquo Journal of Applied PharmaceuticalScience vol 4 no 2 pp 101ndash106 2014
[87] NW Dunham and K R Allard ldquoA preliminary pharmacologicinvestigation of the roots of Bixa orellanardquo Journal of theAmerican Pharmacist Associantion vol 49 pp 218ndash219 1960
[88] F RMedina andRWoodbury ldquoTerrestrial plantsmolluscicidalto lymnaeid hosts of Fasciliasis hepatica in Puerto Ricordquo Journalof Agricultura of the University of Puerto Rico vol 63 pp 366ndash376 1979
[89] B Weniger Y Jiang A Oulad-Ali L Italiano J P Beck and RAnton ldquoBiological effects of bixin and Bixa orellana extracts onlymphoid cells in culturerdquo Planta Medica vol 59 no 7 articleA680 1993
[90] CM Chariandy C E Seaforth R H Phelps G V Pollard andB P S Khambay ldquoScreening of medicinal plants from Trinidad
and Tobago for antimicrobial and insecticidal propertiesrdquoJournal of Ethnopharmacology vol 64 no 3 pp 265ndash270 1999
[91] F J R Paumgartten R R Carvalho I B Araujo et alldquoEvaluation of the developmental toxicity of annatto in the ratrdquoFood and Chemical Toxicology vol 40 no 11 pp 1595ndash16012002
[92] C F Spencer F R Koniuszy E F Rogers et al ldquoSurvey of plantsfor antimalarial activityrdquo Lloydia vol 10 no 3 pp 145ndash174 1947
[93] H Mikkelsen J C Larsen and F Tarding ldquoHypersensitivityreactions to food colours with special reference to the naturalcolour annatto extract (butter colour)rdquo Toxicological Aspects ofFood Safety vol 1 pp 141ndash143 1978
Submit your manuscripts athttpwwwhindawicom
PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom
Volume 2014
ToxinsJournal of
VaccinesJournal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
AntibioticsInternational Journal of
ToxicologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Drug DeliveryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in Pharmacological Sciences
Tropical MedicineJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
AddictionJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Autoimmune Diseases
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Anesthesiology Research and Practice
ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Pharmaceutics
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
10 The Scientific World Journal
[40] F G Coe and G J Anderson ldquoScreening of medicinal plantsused by the Garıfuna of eastern Nicaragua for bioactive com-poundsrdquo Journal of Ethnopharmacology vol 53 no 1 pp 29ndash501996
[41] B Barrett ldquoMedicinal plants of Nicaraguarsquos Atlantic CoastrdquoEconomic Botany vol 48 no 1 pp 8ndash20 1994
[42] G Schmeda-Hirschmann and A R de Arias ldquoA screeningmethod for natural products on triatomine bugsrdquo PhytotherapyResearch vol 6 no 2 pp 68ndash73 1992
[43] G E Simpson ldquoFolk medicine in Trinidadrdquo The Journal ofAmerican Folklore vol 75 no 298 pp 326ndash340 1962
[44] D Mahabir and M C Gulliford ldquoUse of medicinal plants fordiabetes in Trinidad and Tobagordquo Revista Panamericana deSalud Publica vol 1 no 3 pp 174ndash179 1997
[45] E S Ayensu ldquoMedicinal plants of theWest IndiesrdquoUnpublishedManuscript 1978
[46] A Z Mercadante A Steck D Rodriguez-Amaya H Pfanderand G Britton ldquoIsolation of methyl 91015840Z-APO-61015840-lycopenoatefrom Bixa Orellanardquo Phytochemistry vol 41 no 4 pp 1201ndash1203 1996
[47] E Angelucci H K Arima E A Kumagai and I AnnattoldquoPreliminary data of the chemical compositionrdquo Coletanea doInstituto de Tecnologia de Alimentos vol 11 pp 89ndash96 1980
[48] A S L Tirimanna ldquoStudy of the carotenoid pigments of Bixaorellana L Seeds by thin layer chromatographyrdquo MikrochimicaActa vol 76 no 1-2 pp 11ndash16 1981
[49] J M Barbosa-Filho R N Silva-Filho B F Lira et al ldquoTeor debixina em quatro variedades de Bixa orellana L cultivadas naParaıbardquo Revista Brasileira de Farmacognosia vol 7-8 pp 41ndash47 1998
[50] A Z Mercadante A Steck and H Pfander ldquoIsolation andstructure elucidation of minor carotenoids from annatto (Bixaorellana L) seedsrdquo Phytochemistry vol 46 no 8 pp 1379ndash13831997
[51] C Prentice-Hernandez and O Rusig ldquoAnnatto (Bixa orellanaL) extract obtained using ethyl alcohol as a solventrdquo Arquivosde Biologia e Tecnologia vol 35 pp 63ndash74 1992
[52] A Z Mercadante ldquoComposition of carotenoids from annattordquoACS Symposium Series vol 775 pp 92ndash101 2001
[53] M J Scotter L A Wilson G P Appleton and L CastleldquoAnalysis of Annatto (Bixa orellana) Food Coloring Formula-tions 1 Determination of Coloring Components and ColoredThermal Degradation Products by High-Performance LiquidChromatography with Photodiode Array Detectionrdquo Journal ofAgricultural and Food Chemistry vol 46 no 3 pp 1031ndash10381998
[54] A J Degnan J H von Elbe and R W Hartel ldquoExtraction ofannatto seed pigment by supercritical carbon dioxiderdquo Journalof Food Science vol 56 pp 1655ndash1659 1991
[55] A ZMercadante A Steck andH Pfander ldquoIsolation and iden-tification of new apocarotenoids from annatto (Bixa orellana)seedsrdquo Journal of Agricultural and Food Chemistry vol 45 no4 pp 1050ndash1054 1997
[56] S G Anderson M G Nair A Chandra and E MorrisonldquoSupercritical fluid carbon dioxide extraction of annatto seedsand quantification of trans-bixin by high pressure liquid chro-matographyrdquo Phytochemical Analysis vol 8 pp 247ndash249 1997
[57] J M Barbosa-Filho Bixa orellana Retrospectiva de usos pop-ulares atividades biologicas fitoquımica e emprego na fito-cosmetica no continente americano Simposio Brasileiro doUrucummdashSIMBRAU Joao Pessoa Brazil 2006
[58] J Revilla Plantas da Amazonia Oportunidades Economicas eSustentaveis Manaus Programa de Desenvolvimento Empre-sarial e Tecnologico 2nd edition 2001
[59] F Oliveira G Akisue and M K Akisue FarmacognosiaAtheneu Sao Paulo Brazil 1996
[60] J Alonso Tratado de Fitofarmacos y Nutraceuticos CorpusRosario Argentina 2004
[61] C O Franco E G Fabri M Barreiro Neto M H Manfiolli MN C Harder and N C Rucker Urucum Sistema de Producaopara o Brasil Emepa-Pb Apta Joao Pessoa Brazil 2008
[62] P A Venugopalan G A Giridhar and A G RavishankarldquoFood Ethanobotanical and diversified applications of Bixaorellana L a scope for its improvement through biotechnolog-ical mediationrdquo Indian Journal of Fundamental and Applied LifeSciences vol 1 pp 9ndash31 2011
[63] L Taylor Herbal Secrets of the Rainforest Sage Press RocklinCalif USA 2nd edition 2002
[64] J S Oliveira Caracterizacao Extracao e Purificacao por Cro-matografia de Compostos de Urucum (Bixa orellana L) [tesisdoctoral en Ingenierıa Quımic] Universidade Federal de SantaCatarina Florianopolis Brazil 2005
[65] A Z Mercadante A Steck and H Pfander ldquoThree minorcarotenoids from annatto (Bixa orellana) seedsrdquo Phytochem-istry vol 52 no 1 pp 135ndash139 1999
[66] V Galindo-Cuspinera M B Lubran and S A Rankin ldquoCom-parison of volatile compounds in water- and oil-soluble annatto(Bixa orellana L) extractsrdquo Journal of Agricultural and FoodChemistry vol 50 no 7 pp 2010ndash2015 2002
[67] R O Alves de Lima L Azevedo L R Ribeiro and D M FSalvadori ldquoStudy on the mutagenicity and antimutagenicity ofa natural food colour (annatto) in mouse bone marrow cellsrdquoFood and Chemical Toxicology vol 41 no 2 pp 189ndash192 2003
[68] L R P Lima T T Oliveira T J Nagem et al ldquoBixina norbixinae quercetina e seus efeitos no metabolismo lipıdico de coelhosrdquoBrazilian Journal of Veterinary Research andAnimal Science vol38 pp 196ndash200 2001
[69] J D Fontana S V Mendes D S Persike L F Peracetta andM Passos ldquoCarotenoides cores atraentes e acao biologicardquoBiotecnologia Ciencia amp Desenvolvimento vol 2 p 13 2000
[70] C A Penna M Radice G O Gutkind et al ldquoAntibacterial andantifungal activities of some Argentinean plantsrdquo Fitoterapiavol 65 no 2 pp 172ndash174 1994
[71] A M Broussalis G E Ferraro V S Martino R Pinzon J DCoussio and J C Alvarez ldquoArgentine plants as potential sourceof insecticidal compoundsrdquo Journal of Ethnopharmacology vol67 no 2 pp 219ndash223 1999
[72] A Rojas de Arias G Schmeda-Hirschmann and A FalcaoldquoFeeding deterrency and insecticidal effects of plant extracts onLutzomyia longipalpisrdquo Phytotherapy Research vol 6 no 2 pp64ndash67 1992
[73] M S Pinheiro and M Z Rouquayrol ldquoMolluscicidal activityof plants from Northeast Brazilrdquo Revista Brasileira de PesquisasMedicas e Biologicas vol 7 pp 389ndash394 1974
[74] A Hagiwara N Imai T Ichihara et al ldquoA thirteen-week oraltoxicity study of annatto extract (norbixin) a natural food colorextracted from the seed coat of annatto (Bixa orellana L) inSprague-Dawley ratsrdquoFood andChemical Toxicology vol 41 no8 pp 1157ndash1164 2003
[75] C R Almeida R B Silva M J Marques and J K ChavascoldquoEvaluation of antiparasitic activity of hydroethanolic extractsfrom root stem and leaf of Bixa orellana L on Leishmania
The Scientific World Journal 11
amazonensis samplesrdquo Revista da Universidade Vale do RioVerde vol 10 no 2 pp 384ndash391 2012
[76] M V Lopes V C Desoti A D O Caleare T Ueda-NakamuraS O Silva and C V Nakamura ldquoMitochondria superoxideanion production contributes to geranylgeraniol-induced deathin leishmania amazonensisrdquo Evidence-Based Complementaryand Alternative Medicine vol 2012 Article ID 298320 9 pages2012
[77] J M Ferreira D F Sousa M B Dantas et al ldquoEffects of BixaorellanaL seeds onhyperlipidemiardquoPhytotherapyResearch vol27 no 1 pp 144ndash147 2013
[78] P S BenoitHH S FongGH Svoboda andN R FarnsworthldquoBiological and phytochemical evaluation of plants XIV Anti-inflammatory evaluation of 163 species of plantsrdquo Lloydia vol39 no 2-3 pp 160ndash171 1976
[79] D Carabajal A Casaco L Arruzazabala R Gonzalez andV Fuentes ldquoPharmacological screening of plant decoctionscommonly used in Cuban folk medicinerdquo Journal of Ethnophar-macology vol 33 no 1-2 pp 21ndash24 1991
[80] A F C Valdes J M Martınez D A Rodrıguez R S Lizamaand Y G Gaiten ldquoActividad antimalarica de un extractohidroalcoholico de Bixa orellanaLrdquo Revista Cubana de Medic-ina Tropical vol 63 pp 181ndash185 2011
[81] A D Garcıa H R Sanchez and R S Lizama ldquoCitotoxicidadde extractos de plantas medicinales sobre la lınea celularde carcinoma de pulmon humano A549rdquo Revista Cubana deFarmacia vol 45 pp 101ndash108 2011
[82] B Freixa R Vila L Vargas N Lozano T Adzet and SCanigueral ldquoScreening for antifungal activity of nineteen LatinAmerican plantsrdquo Phytotherapy Research vol 12 no 6 pp 427ndash430 1998
[83] A Caceres B Lopez S Gonzalez I Berger I Tada and JMaki ldquoPlants used in Guatemala for the treatment of pro-tozoal infections I Screening of activity to bacteria fungiand American trypanosomes of 13 native plantsrdquo Journal ofEthnopharmacology vol 62 no 3 pp 195ndash202 1998
[84] A Caceres O Cano B Samayoa and L Aguilar ldquoPlants usedin Guatemala for the treatment of gastrointestinal disorders1 Screening of 84 plants against enterobacteriardquo Journal ofEthnopharmacology vol 30 no 1 pp 55ndash73 1990
[85] A S Matsui S Hoskin M Kashiwagi et al ldquoA survey ofnatural products from Hawaii and other areas of the Pacificfor an antifertility effect in micerdquo Internationale Zeitschrift furKlinische PharmakologieTherapie und Toxikologie vol 5 no 1pp 65ndash69 1971
[86] M Abayomi A S Adebayo D Bennett R Porter and JS Campbell ldquoIn vitro antioxidant activity of Bixa orellana(Annatto) seed extractrdquo Journal of Applied PharmaceuticalScience vol 4 no 2 pp 101ndash106 2014
[87] NW Dunham and K R Allard ldquoA preliminary pharmacologicinvestigation of the roots of Bixa orellanardquo Journal of theAmerican Pharmacist Associantion vol 49 pp 218ndash219 1960
[88] F RMedina andRWoodbury ldquoTerrestrial plantsmolluscicidalto lymnaeid hosts of Fasciliasis hepatica in Puerto Ricordquo Journalof Agricultura of the University of Puerto Rico vol 63 pp 366ndash376 1979
[89] B Weniger Y Jiang A Oulad-Ali L Italiano J P Beck and RAnton ldquoBiological effects of bixin and Bixa orellana extracts onlymphoid cells in culturerdquo Planta Medica vol 59 no 7 articleA680 1993
[90] CM Chariandy C E Seaforth R H Phelps G V Pollard andB P S Khambay ldquoScreening of medicinal plants from Trinidad
and Tobago for antimicrobial and insecticidal propertiesrdquoJournal of Ethnopharmacology vol 64 no 3 pp 265ndash270 1999
[91] F J R Paumgartten R R Carvalho I B Araujo et alldquoEvaluation of the developmental toxicity of annatto in the ratrdquoFood and Chemical Toxicology vol 40 no 11 pp 1595ndash16012002
[92] C F Spencer F R Koniuszy E F Rogers et al ldquoSurvey of plantsfor antimalarial activityrdquo Lloydia vol 10 no 3 pp 145ndash174 1947
[93] H Mikkelsen J C Larsen and F Tarding ldquoHypersensitivityreactions to food colours with special reference to the naturalcolour annatto extract (butter colour)rdquo Toxicological Aspects ofFood Safety vol 1 pp 141ndash143 1978
Submit your manuscripts athttpwwwhindawicom
PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom
Volume 2014
ToxinsJournal of
VaccinesJournal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
AntibioticsInternational Journal of
ToxicologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Drug DeliveryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in Pharmacological Sciences
Tropical MedicineJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
AddictionJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Autoimmune Diseases
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Anesthesiology Research and Practice
ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Pharmaceutics
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
The Scientific World Journal 11
amazonensis samplesrdquo Revista da Universidade Vale do RioVerde vol 10 no 2 pp 384ndash391 2012
[76] M V Lopes V C Desoti A D O Caleare T Ueda-NakamuraS O Silva and C V Nakamura ldquoMitochondria superoxideanion production contributes to geranylgeraniol-induced deathin leishmania amazonensisrdquo Evidence-Based Complementaryand Alternative Medicine vol 2012 Article ID 298320 9 pages2012
[77] J M Ferreira D F Sousa M B Dantas et al ldquoEffects of BixaorellanaL seeds onhyperlipidemiardquoPhytotherapyResearch vol27 no 1 pp 144ndash147 2013
[78] P S BenoitHH S FongGH Svoboda andN R FarnsworthldquoBiological and phytochemical evaluation of plants XIV Anti-inflammatory evaluation of 163 species of plantsrdquo Lloydia vol39 no 2-3 pp 160ndash171 1976
[79] D Carabajal A Casaco L Arruzazabala R Gonzalez andV Fuentes ldquoPharmacological screening of plant decoctionscommonly used in Cuban folk medicinerdquo Journal of Ethnophar-macology vol 33 no 1-2 pp 21ndash24 1991
[80] A F C Valdes J M Martınez D A Rodrıguez R S Lizamaand Y G Gaiten ldquoActividad antimalarica de un extractohidroalcoholico de Bixa orellanaLrdquo Revista Cubana de Medic-ina Tropical vol 63 pp 181ndash185 2011
[81] A D Garcıa H R Sanchez and R S Lizama ldquoCitotoxicidadde extractos de plantas medicinales sobre la lınea celularde carcinoma de pulmon humano A549rdquo Revista Cubana deFarmacia vol 45 pp 101ndash108 2011
[82] B Freixa R Vila L Vargas N Lozano T Adzet and SCanigueral ldquoScreening for antifungal activity of nineteen LatinAmerican plantsrdquo Phytotherapy Research vol 12 no 6 pp 427ndash430 1998
[83] A Caceres B Lopez S Gonzalez I Berger I Tada and JMaki ldquoPlants used in Guatemala for the treatment of pro-tozoal infections I Screening of activity to bacteria fungiand American trypanosomes of 13 native plantsrdquo Journal ofEthnopharmacology vol 62 no 3 pp 195ndash202 1998
[84] A Caceres O Cano B Samayoa and L Aguilar ldquoPlants usedin Guatemala for the treatment of gastrointestinal disorders1 Screening of 84 plants against enterobacteriardquo Journal ofEthnopharmacology vol 30 no 1 pp 55ndash73 1990
[85] A S Matsui S Hoskin M Kashiwagi et al ldquoA survey ofnatural products from Hawaii and other areas of the Pacificfor an antifertility effect in micerdquo Internationale Zeitschrift furKlinische PharmakologieTherapie und Toxikologie vol 5 no 1pp 65ndash69 1971
[86] M Abayomi A S Adebayo D Bennett R Porter and JS Campbell ldquoIn vitro antioxidant activity of Bixa orellana(Annatto) seed extractrdquo Journal of Applied PharmaceuticalScience vol 4 no 2 pp 101ndash106 2014
[87] NW Dunham and K R Allard ldquoA preliminary pharmacologicinvestigation of the roots of Bixa orellanardquo Journal of theAmerican Pharmacist Associantion vol 49 pp 218ndash219 1960
[88] F RMedina andRWoodbury ldquoTerrestrial plantsmolluscicidalto lymnaeid hosts of Fasciliasis hepatica in Puerto Ricordquo Journalof Agricultura of the University of Puerto Rico vol 63 pp 366ndash376 1979
[89] B Weniger Y Jiang A Oulad-Ali L Italiano J P Beck and RAnton ldquoBiological effects of bixin and Bixa orellana extracts onlymphoid cells in culturerdquo Planta Medica vol 59 no 7 articleA680 1993
[90] CM Chariandy C E Seaforth R H Phelps G V Pollard andB P S Khambay ldquoScreening of medicinal plants from Trinidad
and Tobago for antimicrobial and insecticidal propertiesrdquoJournal of Ethnopharmacology vol 64 no 3 pp 265ndash270 1999
[91] F J R Paumgartten R R Carvalho I B Araujo et alldquoEvaluation of the developmental toxicity of annatto in the ratrdquoFood and Chemical Toxicology vol 40 no 11 pp 1595ndash16012002
[92] C F Spencer F R Koniuszy E F Rogers et al ldquoSurvey of plantsfor antimalarial activityrdquo Lloydia vol 10 no 3 pp 145ndash174 1947
[93] H Mikkelsen J C Larsen and F Tarding ldquoHypersensitivityreactions to food colours with special reference to the naturalcolour annatto extract (butter colour)rdquo Toxicological Aspects ofFood Safety vol 1 pp 141ndash143 1978
Submit your manuscripts athttpwwwhindawicom
PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom
Volume 2014
ToxinsJournal of
VaccinesJournal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
AntibioticsInternational Journal of
ToxicologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Drug DeliveryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in Pharmacological Sciences
Tropical MedicineJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
AddictionJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Autoimmune Diseases
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Anesthesiology Research and Practice
ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Pharmaceutics
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Submit your manuscripts athttpwwwhindawicom
PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom
Volume 2014
ToxinsJournal of
VaccinesJournal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
AntibioticsInternational Journal of
ToxicologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Drug DeliveryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in Pharmacological Sciences
Tropical MedicineJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
AddictionJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Autoimmune Diseases
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Anesthesiology Research and Practice
ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Pharmaceutics
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of