Review Article Traditional Uses, Chemical Constituents, and ...Francisco Orellana, who was the rst...

12
Review Article Traditional Uses, Chemical Constituents, and Biological Activities of Bixa orellana L.: A Review Daniela de Araújo Vilar, 1 Marina Suênia de Araujo Vilar, 1 Túlio Flávio Accioly de Lima e Moura, 2 Fernanda Nervo Raffin, 2 Márcia Rosa de Oliveira, 3 Camilo Flamarion de Oliveira Franco, 4 Petrônio Filgueiras de Athayde-Filho, 5 Margareth de Fátima Formiga Melo Diniz, 1 and José Maria Barbosa-Filho 1 1 Laboratory of Pharmaceutical Technology, Federal University of Para´ ıba, 58051-900 Jo˜ ao Pessoa, PB, Brazil 2 Department of Pharmacy, Federal University of Rio Grande do Norte, 59010-180 Natal, RN, Brazil 3 Department of Molecular Biology, Federal University of Para´ ıba, 58051-900 Jo˜ ao Pessoa, PB, Brazil 4 State Company of Agricultural Research of Para´ ıba, Rua Eur´ ıpedes Tavares 210, Tambi´ a, 58013-290 Jo˜ ao Pessoa, PB, Brazil 5 Department of Chemistry, Federal University of Para´ ıba, 58051-900 Jo˜ ao Pessoa, PB, Brazil Correspondence should be addressed to Jos´ e Maria Barbosa-Filho; [email protected] Received 11 February 2014; Revised 17 May 2014; Accepted 31 May 2014; Published 23 June 2014 Academic Editor: Tsutomu Hatano Copyright © 2014 Daniela de Ara´ ujo Vilar et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Bixa orellana L., popularly known as “urucum,” has been used by indigenous communities in Brazil and other tropical countries for several biological applications, which indicates its potential use as an active ingredient in pharmaceutical products. e aim of this work was to report the main evidence found in the literature, concerning the ethnopharmacology, the biological activity, and the phytochemistry studies related to Bixa orellana L. erefore, this work comprises a systematic review about the use of Bixa orellana in the American continent and analysis of the data collected. is study shows the well-characterized pharmacological actions that may be considered relevant for the future development of an innovative therapeutic agent. 1. Introduction e use of natural compounds of mineral, animal, or plant origin in food products, cosmetics, and drugs began long ago. ere are written records of ancient Egyptian and Chinese civilizations that have made use of these products. Nowadays, there has been a return to the search for products called “natural,” which in fact never ceased to exist. e analysis of the composition of many drugs shows that almost 50% of those in clinical use are derived from natural compounds. Furthermore, not only plants but also plant byproducts are widely used as preservatives and flavoring and coloring agents in various food and cosmetic preparations [1]. Bixa orellana is a plant native to Brazil but grows in other regions of South and Central America. It is grown in tropical countries such as Peru, Mexico, Ecuador, Indonesia, India, Kenya, and East Africa [2]. e seeds of this plant produce one of the dyes most frequently used worldwide, not only in food products but also in the textile, paint, and cosmetic industries. Its use has been stimulated due to the ban on the use of synthetic dyes in food and cosmetics, where it is one of the few accepted by the World Health Organization (WHO), since, in addition to being nontoxic, it does not seem to change the food value [3]. Another interesting fact is that 70% of all natural coloring agents consumed worldwide are derived from annatto [4]. Annatto first spread in the form of food coloring, also known as paprika, a condiment widely used in cooking to enhance the color of food. Today, however, its use has spread into many segments of industrial production. us, it is now applied on the skin—in the form of makeup and sunscreen— and there is research proving that its use brings health benefits, which makes producers thankful for cultivating it [5, 6]. erefore, in the continuation of our research on Hindawi Publishing Corporation e Scientific World Journal Volume 2014, Article ID 857292, 11 pages http://dx.doi.org/10.1155/2014/857292

Transcript of Review Article Traditional Uses, Chemical Constituents, and ...Francisco Orellana, who was the rst...

Page 1: Review Article Traditional Uses, Chemical Constituents, and ...Francisco Orellana, who was the rst European to navigate theAmazon[ ]. According to Revilla [ ], B. orellana is a small

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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Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

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AntibioticsInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Medicinal ChemistryInternational Journal of

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Autoimmune Diseases

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Pharmaceutics

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MEDIATORSINFLAMMATION

of

Page 2: Review Article Traditional Uses, Chemical Constituents, and ...Francisco Orellana, who was the rst European to navigate theAmazon[ ]. According to Revilla [ ], B. orellana is a small

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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of

Page 3: Review Article Traditional Uses, Chemical Constituents, and ...Francisco Orellana, who was the rst European to navigate theAmazon[ ]. According to Revilla [ ], B. orellana is a small

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

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Page 4: Review Article Traditional Uses, Chemical Constituents, and ...Francisco Orellana, who was the rst European to navigate theAmazon[ ]. According to Revilla [ ], B. orellana is a small

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

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

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Medicinal ChemistryInternational Journal 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

Page 5: Review Article Traditional Uses, Chemical Constituents, and ...Francisco Orellana, who was the rst European to navigate theAmazon[ ]. According to Revilla [ ], B. orellana is a small

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

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Page 6: Review Article Traditional Uses, Chemical Constituents, and ...Francisco Orellana, who was the rst European to navigate theAmazon[ ]. According to Revilla [ ], B. orellana is a small

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

Volume 2014

ToxinsJournal of

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Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

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MEDIATORSINFLAMMATION

of

Page 7: Review Article Traditional Uses, Chemical Constituents, and ...Francisco Orellana, who was the rst European to navigate theAmazon[ ]. According to Revilla [ ], B. orellana is a small

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

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

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Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Autoimmune Diseases

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Anesthesiology Research and Practice

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Pharmaceutics

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MEDIATORSINFLAMMATION

of

Page 8: Review Article Traditional Uses, Chemical Constituents, and ...Francisco Orellana, who was the rst European to navigate theAmazon[ ]. According to Revilla [ ], B. orellana is a small

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

Page 9: Review Article Traditional Uses, Chemical Constituents, and ...Francisco Orellana, who was the rst European to navigate theAmazon[ ]. According to Revilla [ ], B. orellana is a small

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

Page 10: Review Article Traditional Uses, Chemical Constituents, and ...Francisco Orellana, who was the rst European to navigate theAmazon[ ]. According to Revilla [ ], B. orellana is a small

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

Page 11: Review Article Traditional Uses, Chemical Constituents, and ...Francisco Orellana, who was the rst European to navigate theAmazon[ ]. According to Revilla [ ], B. orellana is a small

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

Page 12: Review Article Traditional Uses, Chemical Constituents, and ...Francisco Orellana, who was the rst European to navigate theAmazon[ ]. According to Revilla [ ], B. orellana is a small

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