review ethnopharmacology of lippia alba lippa - lippia alba/ethnopharm… · available online at...

A

IiErCaBaCio©

K

C

0d

Available online at www.sciencedirect.com

Journal of Ethnopharmacology 116 (2008) 211–222

Review

Ethnopharmacology of Lippia alba

Thierry Hennebelle a, Sevser Sahpaz a, Henry Joseph b, Francois Bailleul a,∗a Laboratoire de Pharmacognosie, E.A. 1043, Universite de Lille 2, Faculte de Pharmacie B.P. 83, 59006 Lille cedex, France

b Association pour la promotion des PLAntes MEDicinales et AROMatiques (APLAMEDAROM) de Guadeloupe,F-97142 Les Abymes, Guadeloupe, France

Received 10 October 2007; received in revised form 29 November 2007; accepted 29 November 2007Available online 8 December 2007

bstract

ntroduction: Chemical, ethnopharmacological and pharmacological research on Lippia alba (Mill.) N.E. Brown and the evidence that exists forts various usages have been looked for, focusing on high quality studies.thnopharmacological investigation: The species is mainly used against digestive and respiratory ailments, and as a sedative and antihypertensive

emedy.hemical constituents: Seven chemotypes exist for the essential oil, the non-volatile compounds are iridioids, phenylethanoids, flavone glycosidesnd biflavonoids.iological activities and ethnopharmacological appraisal: Some positive, although partial, results have been obtained on sedative and anxiolyticctivities. Real effects in other traditional uses can mainly be explained by anti-infectious and analgesic properties, at the moment.
onclusion: Well conducted biological studies are still needed for several indications of this species. Its use as a sedative deserves a clinical
nvestigation. The chemical variability of the species seems important both in the essential oil and in non-volatile compounds, so future researchn the pharmacological properties of these extracts should provide more chemical data which will increase their validity.

2007 Elsevier Ireland Ltd. All rights reserved.

eywords: Lippia alba; Verbenaceae; Digestive; Respiratory; Sedative; Hypertension; Anti-infectious

ontents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2122. Botanical data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2123. Ethnopharmacological investigation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2134. Chemical constituents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2135. Biological investigation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214

5.1. Anti-infectious properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2155.1.1. Antibacterial and antifungal activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2155.1.2. Antiviral activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
5.1.3. Antiprotozoal activity . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2. Effects on the nervous system . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5.2.1. Neurosedative activity . . . . . . . . . . . . . . . . . . . . . . . . . . . .5.2.2. Analgesic and anti-inflammatory activities . . . . . . . . .

Abbreviations: AFSSaPS, Agence Francaise pour la Securite Sanitaire des Provirus; DPPH, 1,1-diphenyl-2-picrylhydrazyl; EC50, effective concentration 50%; HIVconcentration 50%; LD50, lethal dose 50%; MIC, minimal inhibitory concentration; Ltetrazolium bromide; NCI, National Cancer Institute; PMA, phorbol myristate acetate;for the IsLands; VSV, vesicular stomatitis virus.

∗ Corresponding author. Tel.: +33 320 964039; fax: +33 320 964039.E-mail address: [email protected] (F. Bailleul).

378-8741/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved.oi:10.1016/j.jep.2007.11.044

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219

duits de Sante; BHA, butyl-hydroxyanisole; BVDV, bovine viral diarrhoea, human immunodeficiency virus; HSV, herpes simplex virus; IC50, inhibitingSU, level of significative use; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl

TEAC, trolox equivalent antioxidant capacity; TRAMIL, TRAditional Medicine

mailto:[email protected]

dx.doi.org/10.1016/j.jep.2007.11.044

212 T. Hennebelle et al. / Journal of Ethnopharmacology 116 (2008) 211–222

5.3. Cardiovascular activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2205.4. Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220

5.4.1. Antioxidant activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2205.4.2. Cytotoxic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220

6. Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2207. Ethnopharmacological appraisal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2208. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221

. . . . .

1

iSldttsFmtahas(2iPpaeAc

2

npioAAntochcaRa22

hopcweH

pVthe variability of the species and more generally in the com-plexities inherent in the Verbenaceae family. Seven infraspecifictaxa of the species Lippia alba (Mill.) N.E. Brown have beenestablished: Lippia alba f. alba Moldenke, Lippia alba f. inter-

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. Introduction

Lippia alba (Mill.) N.E. Brown is an aromatic shrub belong-ng to the Verbenaceae family, which is widely used all overouth and Central America for different purposes. In particu-

ar, Lippia alba has been used for centuries in French overseasepartments (French Guiana, Guadeloupe, Martinique) despitehe fact that, when slavery was still authorised in France (that iso say until 1848), black slaves did not have the right to use orell medicinal plants, lest they poisoned white settlers. As therench Pharmacopeia was created during the slavery period, noedicinal plants from the overseas departments were included at

hat time, except for those used by white people. In spite of thebolition of slavery, traditional remedies of black populationsad no official status until very recently. Lippia alba and Sennalata (L.) Roxb. (Fabaceae) were the first two plants from over-eas departments to be approved by the French Drug AgencyAFSSaPS) for inclusion in the French Pharmacopeia (Robard,003). This work is also of interest because of the impendingnscription of Lippia alba in European (French and Spanish)harmacopeias. The aim of this work is to list and compareapers that have dealt with ethnopharmacological, biologicalnd pharmacological studies of this species, so as to synthesisexisting scientific evidence on the different uses of this plant.

discussion of the available data on activities and chemicalomposition ensues.

. Botanical data

Lippia alba (Mill.) N.E. Brown (Fig. 1) belongs to the Verbe-aceae family, which also includes other medicinally importantlants like Aloysia triphylla (L’Herit.) Britt. and Verbena offic-nalis L. Lippia alba is abundantly present between the southf the United States of America (Florida) and the north ofrgentina. It is also present in India (Singh et al., 2000) andustralia (Day and Mc Andrew, 2003). The local and traditionalames are numerous in Latin America, because of widespreadraditional use, and are generally derived from its aromatic smellr medicinal properties. The most common name in Brazil isidreira, but this can also be used for 17 other lemon-scentederbs with similar uses (Matos et al., 1996). In Spanish-speakingountries and French overseas departments, it is often namedfter other aromatic species, e.g.: salvia morada (Senatore and
igano, 2001), oregano de cerro (Stashenko et al., 2003),nıs de Espana (Pino Alea et al., 1996), mirto (Alanıs et al.,005), verveine blanche, sauge du Bresil (Sastre and Breuil,007).
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221

It is a shrub, with a quadrangular branch, reaching 1.7 m ineight. The leaves are membranaceous, petiolate, pubescent,pposite or ternate, and its limb shows variable forms with aointed apex, cuneiform or decumbent basis and serrated orrenated border (except on the basis). The flowers (3–5 mm) arehite or pink. The fruit is composed of two indehiscent nucleus,

ach containing one brown seed (Adams, 1972; Fournet, 2002;oward, 1989).An incredible number of synonyms are to be found for Lip-

ia alba. They belong to the genera Lippia, Lantana, Phyla,erbena and Zapania (ISB, 2007). The explanation may lie in

Fig. 1. Lippia alba (Mill.) N.E. Brown (Verbenaceae) (photograph by H.J.).

hnoph

maMv

3

stwieEat

Pe(mwi(osa(aiih1Bdoup

csatcutc(Lveb(tPta

adMfwsf(a2

calaacp

4

vooooipBmilrptccpseat

plt(aslp

T. Hennebelle et al. / Journal of Et

edia Moldenke, Lippia alba f. macrophylla Moldenke, Lippialba f. scabra Moldenke, Lippia alba var. globiflora (L’Her.)oldenke, Lippia alba var. carterae Moldenke and Lippia alba

ar. lanceolata (Griseb.) Mulgura (IPNI, 2007).

. Ethnopharmacological investigation

Numerous papers have presented ethnopharmacologicaltudies dealing with Lippia alba (among other plants). A selec-ion of these studies is presented here. Cited papers (excepthere noted) have been selected on the basis of their qual-

ty, in accordance with the criteria for ethnopharmacology andthnobotanical studies in the “Rules of 5” of the Journal ofthnopharmacology (Verpoorte et al., 2006), with a specialttention to the use of frequency of citation (or related quan-itative parameter).

A study, performed around three cities in the state of Saoaulo, showed a widespread use of Lippia alba: it was the sev-nth most cited species by plant users and traditional healers29.5%). Leaves are used as an infusion against states of excite-ent, hypertension, digestive troubles, nausea and cold, to healounds locally and as a syrup against cough and bronchitis. An

nfusion of the roots is also used against bad colds and coughsDi Stasi et al., 2002). In two studies carried out in the statef Bahia, Lippia alba was one of the two most frequently citedpecies. In the village of Sapucaia, Cruz das Almas, it is useds a sedative and also against hypertension, flatulence and painRodrigues and Guedes, 2006). In Itacare, it is used against stom-ch ache and digestive troubles with high concordance betweennformants (Pinto et al., 2006). In a Mixe community, in Mex-co, the leaves of Lippia alba were frequently cited by traditionalealers as active against gastrointestinal troubles (Heinrich et al.,992). In San Isidro, in the municipality of San Jose de Pare-oyaca, Colombia, Lippia alba is used as a painkiller, againstigestive troubles, diarrhea, stomach pain, flu and cough. It isne of the ten species with the highest LSU (level of significativese), according to TRAMIL: it was cited by 20% of interviewedeople (Toscano-Gonzalez, 2006).

In the papers mentioned above, Lippia alba has always beenonsidered as very useful, and is frequently one of the most citedpecies. In contrast, in the following surveys, although Lippialba appears, it seems to be of relatively little interest, quanti-atively speaking. In the Quilombola de Olho D’agua dos Piresommunity, in Esperantina (Brazil), an infusion of the leaves issed against sore throat and flu (Franco and Barros, 2006). Inhe municipality of Igarassu (state of Pernambuco), local spe-ialists use Lippia alba against anaemia and digestive troublesGazzaneo et al., 2005). In the Afro-Caribbean community ofivingston (Guatemala), the leaves of Lippia alba are used inarious forms against cough (decoction as a beverage), skin dis-ases (macerate is used for washing), flatulence (infusion as aeverage), nausea and vomiting (the plant is smoked), headachesthe plant is crushed and used as a poultice). The oral route is
he most frequently cited (Giron et al., 1991). In Ponta Grossa,orto Alegre (Brazil), although Lippia alba is rather rarely men-
ioned (low use value), the consistency of the use of its leaves assedative is considered as good (Vendruscolo and Mentz, 2006).

tcvf

armacology 116 (2008) 211–222 213

One survey was specifically dedicated to the species Lippialba. Near Oriximina (state of Para, Brazil), people use twoifferent infraspecific taxa of Lippia alba: Lippia alba f. albaoldenke (erva-cidreira), which is cultivated, and Lippia alba

. intermedia Moldenke (carmelitana), which is harvested in theild at certain periods of the year. Both were cited as having

edative and digestive properties, but the major use agreementor cidreira was far better (MUA = 92.0%) than for carmelitanaMUA = 66.7%). Lippia alba f. alba has sometimes been usedgainst respiratory ailments and hypertension (Oliveira et al.,006).

The main medicinal usages found in these selected well-onducted ethnopharmacological surveys (see Table 1) are inccordance with those that are cited in other ethnopharmaco-ogical studies and in other papers or books. The four main usesre against digestive, respiratory, cardiovascular troubles and assedative medicine. Nevertheless, numerous other usages are

ited and the versatility of this plant makes it a species of highotential economic interest (Albuquerque et al., 2007a,b).

. Chemical constituents

Most of the investigators studied the essential oil, by con-entional methods of analysis, i.e. gas chromatography, in mostf the cases coupled with mass spectrometry. The compositionf the essential oil is very variable, suggesting the existencef a high number of chemotypes. We have recently endeav-ured to establish a system classifying all published analysesn seven chemotypes, on the basis of the composition and ofossible common biosynthetic pathways between different oils.riefly, chemotype I had citral, linalool, �-caryophyllene as theain constituents (four subtypes); in the case of chemotype II,

t was tagetenone; the most common case for chemotype III wasimonene with a variable amount of carvone, but biosyntheticallyelated monoterpenic ketones (i.e. dihydrocarvone, piperitone,iperitenone) could be found instead of carvone (two subtypes);he four other chemotypes corresponded to isolated analyses:hemotypes IV (myrcene), V (�-terpinene), VI (camphor-1,8-ineole) and VII (estragole) (Hennebelle et al., 2006a). Since theublication of this classification, we have found two new analy-es of the essential oil of Lippia alba (Barbosa et al., 2006b; Silvat al., 2006): in both cases, citral was the major compound, withlow amount of linalool (<5%), both therefore corresponding

o subtype Ia.In the case of structural characterisation of non-volatile com-

ounds of Lippia alba, most investigators have studied theeaves. The presence of three iridoids, geniposide (1, Fig. 2),heveside (2) and shanzhizide methyl ester (3), was reportedHeinrich et al., 1992; Von Poser et al., 1997; Barbosa etl., 2006a). All three compounds were found again in onetudy, along with geniposidic acid (4), caryoptoside (5), 8-epi-oganin (6) and mussaenoside (7) (Hennebelle et al., 2006b). Thehenyletanoid/phenylpropanoid constituents characterised by
wo different groups were isonuomioside (8), decaffeoylverbas-oside (9) (Barbosa et al., 2006a), verbascoside (10), 2′′-acetylerbascoside (11), isoverbascoside (12), calceolarioside E (13),orsythoside B (14) and cistanoside F (15). The flavonoid

214 T. Hennebelle et al. / Journal of Ethnopharmacology 116 (2008) 211–222

Table 1Reported uses of Lippia alba in ethnopharmacological surveys

Type of use Population or geographic zone Part used and method References

Digestive Digestive troubles ingeneral

Vale do Ribeira, state of Sao Paulo (Brazil) Leaves, infusion Di Stasi et al. (2002)Igarassu, state of Pernambuco (Brazil) Leaves, n.r. Gazzaneo et al. (2005)Oriximina, state of Para (Brazil) Leaves of Lippia alba f. alba,

leaves and flowers of Lippia albaf. intermedia, infusion ordecoction

Oliveira et al. (2006)

San Jose de Pare-Boyaca (Colombia) n.r. Toscano-Gonzalez (2006)Itacare, Bahia State (Brazil) n.r. Pinto et al. (2006)

Nausea and/or vomiting Vale do Ribeira, state of Sao Paulo (Brazil) Leaves, infusion Di Stasi et al. (2002)Livingston (Guatemala) Leaves, smoking Giron et al. (1991)

Stomach pain Mixe, Oaxaca, Tehuantepec isthmus(Mexico)

Leaves Heinrich et al. (1992)

San Jose de Pare-Boyaca (Colombia) n.r. Toscano-Gonzalez (2006)Itacare, Bahia State (Brazil) n.r. Pinto et al. (2006)

Flatulence Sapucaia, state of Bahia (Brazil) n.r. Rodrigues and Guedes (2006)Livingston (Guatemala) Leaves, infusion Giron et al. (1991)

Diarrhea San Jose de Pare-Boyaca (Colombia) n.r. Toscano-Gonzalez (2006)

Respiratory Respiratory ailments ingeneral

Oriximina, state of Para (Brazil) Leaves of Lippia alba f. alba,infusion or decoction


Bronchitis Vale do Ribeira, state of Sao Paulo (Brazil) Leaves, syrup Di Stasi et al. (2002)Sore throat Quilombola de Olho D’agua dos Pires,

Esperantina, state of Piauı (Brazil)Leaves, infusion Franco and Barros (2006)

Flu Quilombola de Olho D’agua dos Pires,Esperantina, state of Piauı (Brazil)

Leaves, infusion Franco and Barros (2006)

San Jose de Pare-Boyaca (Colombia) n.r. Toscano-Gonzalez (2006)Cough Livingston (Guatemala) Leaves, decoction Giron et al. (1991)

Vale do Ribeira, state of Sao Paulo (Brazil) Leaves, syrup Di Stasi et al. (2002)Roots, infusion

San Jose de Pare-Boyaca (Colombia) n.r. Toscano-Gonzalez (2006)Cold Vale do Ribeira, state of Sao Paulo (Brazil) Leaves, infusion Di Stasi et al. (2002)

Sedative Vale do Ribeira, State of Sao Paulo (Brazil) Leaves, infusion Di Stasi et al. (2002)Sapucaia, state of Bahia (Brazil) n.r. Rodrigues and Guedes (2006)Pontes e Lacerda and Comodo (state of MatoGrosso)

Leaves, infusion or syrup Coelho and da Silva (2003)

Oriximina, state of Para (Brazil) Leaves of Lippia alba f. alba,leaves and flowers of Lippia albaf. intermedia, infusion ordecoction


Ponta Grossa, Porto Alegre (Brazil) Leaves Vendruscolo and Mentz (2006)

Cardiovascular Hypertension Vale do Ribeira, state of Sao Paulo (Brazil) Leaves, infusion Di Stasi et al. (2002)Sapucaia, state of Bahia (Brazil) n.r. Rodrigues and Guedes (2006)Oriximina, state of Para (Brazil) Leaves of Lippia alba f. alba,

infusion or decoctionOliveira et al. (2006)

Miscellaneous Anemia Igarassu, state of Pernambuco (Brazil) Leaves, n.r. Gazzaneo et al. (2005)Headache Livingston (Guatemala) Leaves, poultice Giron et al. (1991)Pain Sapucaia, state of Bahia (Brazil) n.r. Rodrigues and Guedes (2006)

San Jose de Pare-Boyaca (Colombia) n.r. Toscano-Gonzalez (2006)

aulo (

n

g7((w

ci(

5

Lo

Skin diseases Livingston (Guatemala)Wounds Vale do Ribeira, state of Sao P

.r.: not recorded.

lycosides so far known to occur in the leaves are apigenin--glucuronide (16), luteolin-7-glucuronide (17), clerodendrin18), luteolin-7-diglucuronide (19) and 3′′′-acetylclerodendrin20) (Hennebelle et al., 2006b). Two biflavonoids (21, 22, Fig. 2)ere also isolated (Barbosa et al., 2005).
Only one work so far has been dedicated to the chemical
omposition of the roots of Lippia alba and led to the character-sation of mussaenoside, theviridoside (23) and gardoside (24)Sena Filho et al., 2007).

cawa

Leaves, macerate for washing Giron et al. (1991)Brazil) Leaves, local use Di Stasi et al. (2002)

. Biological investigation

Lippia alba is probably one of the most studied species in theippia genus from a pharmacological point of view. The subjectsf experimental works performed on this species are generally
onsistent with its traditional uses. Because of the chemical vari-bility of the plant the main identified compound(s) is (are) citedhen available. Papers were selected on the basis of the use of
ppropriate positive controls.

T. Hennebelle et al. / Journal of Ethnopharmacology 116 (2008) 211–222 215

l cons

5

5

estat0rtiMm

wscvmwmwlw

Fig. 2. Isolated chemica

.1. Anti-infectious properties

.1.1. Antibacterial and antifungal activityAntiseptic activity has been the most studied field of inter-

st for Lippia alba. Antibacterial and antifungal activities perpecies are shown in Table 2. Only one study totally respectedhe criteria of the “Rules of 5”, applied since 2006 (Verpoorte etl., 2006) in the Journal of Ethnopharmacology: a positive con-rol was used and the MIC of both an essential oil (76% linalool;.60 mg/ml) and a positive control (nistatin; 0.05 mg/ml) wereeported (Duarte et al., 2005). In other works, the determina-
ion of MIC was lacking (with only a determination of growthnhibition zone, in comparison with a positive control) or the
IC of the positive control was not given (although its use wasentioned).

Nwa(

tituents of Lippia alba.

There is no agreement on the level of acceptance for planthen compared with standards; therefore, some authors con-

ider only activity comparable to antibiotics, while othersonsider even higher values. It has been suggested that an MICalue of 100–200 �g/ml could be considered as good for plantaterial (Borges-Argaez et al., 2007). Such values were reachedith various root extracts against Micrococcus luteus (acetone,ethanol, chloroform) and Bacillus subtilis (chloroform) andith ethanol or hydroethanolic leaf extracts against Micrococcus

uteus and Candida krusei (Aguiar, 2006; Holetz et al., 2002),hich are not frequent pathogens in immunocompetent humans.
evertheless, slightly higher MIC values (250–500 �g/ml)ere obtained with a 40% carvone essential oil, acetone
nd chloroform root extracts against Staphylococcus aureusAguiar, 2006; Pino Alea et al., 1996). Moderate activities

216T.H

ennebelleetal./JournalofE

thnopharmacology

116(2008)

211–222Table 2Antibacterial and antifungal activities of essential oils and extracts of Lippia alba

Classification Species Tested material MIC (mg/ml) Other results References

BacteriaBacilli Gram + Bacillus subtilis EO (40% carvone, 10% �-guaiene, 6%

limonene)0.63 MBC = 1.25 mg/ml Pino Alea et al. (1996)

90% ethanol leaf extract (48 h) >1 Holetz et al. (2002)Hexane, ethanol and methanol leaf extracts(8 days)

n.r. GIZ (2000 �g/disc) < Ka(30 �g/disc)

Aguiar (2006)

Acetone and ethanol root extracts (8 days) 0.25Chloroform root extract (8 days) 0.0312

Lactobacillus casei EO (37% citral, 15% myrcene, 5% geraniol,5% germacrene D)

n.r. GIZ (5 �L/disc) > V, M(10 �g/disc)


EO (22% citral, 10% nerol, 6% geraniol) n.r.

Cocci Gram + Enterococcus faecalis Ethyl acetate, methanol and water rootextracts (48 h, r.t.)

n.r. GI “−” (50 and 100 mg/ml) Sena Filho et al. (2006)

Hexane, ethanol and methanol leaf extracts,chloroform, acetone and ethanol rootextracts (8 days)

n.r. GI “−”(2000 �g/disc) Aguiar (2006)

EO (40% carvone, 10% �-guaiene, 6%limonene)

0.63 MBC = 1.25mg/ml Pino Alea et al. (1996)

Micrococcus luteus Ethanol leaf extract (8 days) 0.0625 GIZ (2000 �g/disc) < Ka(30 �g/disc)

Aguiar (2006)

Hexane leaf extract (8 days) 0.5Methanol leaf extract (8 days) 0.25Acetone and ethanol root extracts (8 days) 0.125Chloroform root extract (8 days) 0.0312

Staphylococcus aureus EO (40% carvone, 10% �-guaiene, 6%limonene)

0.31 MBC = 0.63 mg/ml Pino Alea et al. (1996)

EO (37% citral, 15% myrcene, 5% geraniol,5% germacrene D)

n.r. GIZ > V, M Oliveira et al. (2006)

EO (22% citral, 10% nerol, 6% geraniol) n.r. GIZ ≤ V, M90% ethanol leaf extract (48 h) >1 Holetz et al. (2002)Hexane, ethanol and methanol leaf extracts(8 days)


Aguiar (2006)

Acetone root extract (8 days) 0.25Chloroform root extract (8 days) 0.5Ethanol root extract (8 days) 1Ethyl acetate root extract (48 h, r.t.) 0.5; 1 GIZ ≥ 11 mm (“+”) at

50 mg/ml, < T 1 mg/mlSena Filho et al. (2006)

Methanol root extract (48 h, r.t.) ≥2 GI + at 100 mg/ml, < T1 mg/ml

Aqueous root extract (48 h, r.t.) n.r. GI “−” (50 and 100 mg/ml)Staphylococcus aureus MRSA(BMB9393)


n.r. GIZ (5 �L/disc) ≥ V, M(10 �g/disc)


EO (22% citral, 10% nerol, 6% geraniol) n.r. GIZ (5 �L/disc) > V, M(10 �g/disc)

T.Hennebelle

etal./JournalofEthnopharm

acology116

(2008)211–222

217

Staphylococcus epidermidis EO (40% carvone, 10% �-guaiene, 6%limonene)

0.63 MBC = 1.25 mg/ml Pino Alea et al., 1996

Streptococcus mutans EO (37% citral, 15% myrcene, 5% geraniol,5% germacrene D)

n.r. GIZ (5 �L/disc) > V, M(10 �g/disc)



Bacilli Gram - Enterobacter aerogenes EO (40% carvone, 10% �-guaiene, 6%limonene)

2.5 2.5 mg/ml Pino Alea et al. (1996)

Escherichia coli EO (40% carvone, 10% �-guaiene, 6%limonene)

2.5 2.5 mg/ml Pino Alea et al. (1996)

90% ethanol leaf extract (48 h) >1 Holetz et al. (2002)Aqueous (decoction, 3 h) and methanol (timeunknown) leaf extracts

n.r. GI 8 mg/ml < 50% (“−”) Alanıs et al. (2005)

Ethyl acetate, methanol and water rootextracts (48 h, r.t.)


Hexane, ethanol and methanol leaf extracts,chloroform, acetone and ethanol rootextracts (8 days)


Klebsiella pneumoniae EO (40% carvone, 10% �-guaiene, 6%limonene)


Ethyl acetate and methanol root extracts(48 h, r.t.)

>2 GI + at 100 mg/ml ethylacetate extract, < T 1 mg/ml

Sena Filho et al. (2006)

Aqueous root extract (48 h, r.t.) n.r. GI “−” (50 and 100 mg/ml)Pseudomonas aeruginosa EO (40% carvone, 10% �-guaiene, 6%

limonene)R Pino Alea et al. (1996)

90% ethanol leaf extract (48 h) >1 Holetz et al. (2002)Aqueous root extract (48 h, r.t.) n.r. GI “−” (50 and 100 mg/ml) Sena Filho et al. (2006)Hexane, ethanol, methanol leaf extracts,chloroform, acetone, ethanol root extracts (8days)


Salmonella sp. Aqueous (decoction, 3 h) and methanol (timeunknown) leaf extracts

n.r. GI < 50% (“−”) Alanıs et al. (2005)

Ethyl acetate, methanol and water rootextracts (48 h, r.t.)


Serratia marcescens EO (40% carvone, 10% �-guaiene, 6%limonene)


Hexane, ethanol, methanol leaf extracts,chloroform, acetone, ethanol root extracts (8days)


Shigella flexneri Aqueous (decoction, 3 h) and methanol (timeunknown) leaf extracts

n.r. GI < 50% (“−”) Alanıs et al. (2005)

Shigella sonnei Aqueous (decoction, 3 h) and methanol (timeunknown) leaf extracts

n.r. GI < 50% (“−”) Alanıs et al. (2005)

Mycobacteria Mycobacterium smegmatis Hexane, ethanol, methanol leaf extracts,chloroform, acetone, ethanol root extracts (8days)


Aguiar (2006)

Mycobacterium tuberculosis 95% ethanol leaf extract n.r. 82% inhibition at 100 �g/ml(“−”), PC = 1 �g/mlRi

Antoun et al. (2001)

218T.H

ennebelleetal./JournalofE

thnopharmacology

116(2008)

211–222Table 2 (Continued )

Classification Species Tested material MIC (mg/ml) Other results References

95% ethanol stem extract n.r. 19% inhibition at 100 �g/ml(“−”), PC = 1 �g/mlRi

FungiCandida albicans EO (76% linalool) 0.60 (nistatin: 0.05) Duarte et al. (2005)

70% ethanol leaf extract (2 × 3 h, agitation) REO (37% citral, 15% myrcene, 5% geraniol,5% germacrene D)

n.r. GIZ (5 �L/disc) > AB(10 �g/disc)


EO (22% citral, 10% nerol, 6% geraniol) n.r.90% ethanol leaf extract (48 h) >1 Holetz et al. (2002)Hexane, ethanol and methanol leaf extracts(8 days)


Acetone and ethanol root extracts (8 days) n.r. GIZ (2000 �g/disc) < Ke(300 �g/disc)

Chloroform root extract (8 days) 2Candida albicans serotype B EO (37% citral, 15% myrcene, 5% geraniol,

5% germacrene D)n.r. GIZ (5 �L/disc) > AB

(10 �g/disc)Oliveira et al. (2006)

EO (22% citral, 10% nerol, 6% geraniol) n.r.Candida guilliermondii EO (37% citral, 15% myrcene, 5% geraniol,

5% germacrene D)n.r.

EO (22% citral, 10% nerol, 6% geraniol) n.r.Candida krusei 90% ethanol leaf extract (48 h) 0.125 Holetz et al. (2002)Candida parapsilosis EO (37% citral, 15% myrcene, 5% geraniol,



EO (22% citral, 10% nerol, 6% geraniol) n.r. GIZ (5 �L/disc) ≤ AB(10 �g/disc)

90% ethanol leaf extract (48 h) >1 Holetz et al. (2002)Candida tropicalis 90% ethanol leaf extract (48 h) >1Chrysonilia sitophila Hexane, ethanol, methanol leaf extracts,

acetone, ethanol root extracts (8 days)n.r. GI “−”(2000 �g/disc) Aguiar (2006)

Chloroform root extract (8 days) n.r. GIZ (2000 �g/disc) < Ke(300 �g/disc)

Cryptococcus neoformansT1-444 Serotype A




EO (22% citral, 10% nerol, 6% geraniol) n.r.Fonsecaea pedrosoi 5VPL EO (37% citral, 15% myrcene, 5% geraniol,



EO (22% citral, 10% nerol, 6% geraniol) n.r. GIZ (5 �L/disc) ≤ AB(10 �g/disc)

Trichophyton rubrum T544 EO (37% citral, 15% myrcene, 5% geraniol,5% germacrene D)




AB: amphothericin B; EO: essential oil; GI: growth inhibition; GIZ: growth inhibition zone; Ka: kanamycin; Ke: ketoconazole; M: methicillin; MBC: minimal bactericidal concentration; n.r.: not recorded; PC:positive control; R: resistant; Ri: rifampicin; r.t.: room temperature; T: tetracycline; V: vancomycin. In the case of Alanıs et al. (2005), the positive control was trimethoprim (8 mg/ml), which inhibited 100% ofbacterial growth, except against Shigella sonnei.

hnoph

(edM(i2

5

raatTVlmvat((eHtea2

5

u1waTilst

5

5

i�ccbedpfit2

htapt

ahppriditbprabapwmt(ma

5

gcl8wwwwtlot5wmla

raim


MIC = 600–630 �g/ml) were observed against Staphylococcuspidermidis, Enterococcus faecalis, Serratia marcescens, Can-ida albicans (Pino Alea et al., 1996; Duarte et al., 2005).oreover, the growth inhibition zone of citral essential oils

5 �L/disc) was superior to that of vancomycin (10 �g/disc)n methicillin-resistant Staphylococcus aureus (Oliveira et al.,006).

.1.2. Antiviral activityOnly extracts of Lippia alba were used to evaluate antivi-

al activities. An ethanolic extract exhibited anti-HSV-1 effectt 12.5 to 50 �g/ml, obtained by assessing cytopathic effectnd protein synthesis ([35S]methionine incorporation), but alsooxicity against HeLa cells at the higher tested concentrations.he same extract was ineffective against poliovirus type 1 andSV (Abad et al., 1997). A methanolic extract made from

eaves and twigs did not show any activity against BVDV-1 (aodel of anti-HCV activity), HSV-1, HSV-2, HIV and influenza

irus type A, whereas an infusion of the ground material hadselectivity index (cytotoxic concentration/antiviral concen-

ration ratio) of 19.2 against influenza virus type A (H3N2)EC50 = 122.7 �g/ml) (Ruffa et al., 2004). Of the three fractionsdichloromethane, ethyl acetate and butanol) obtained from anthanolic extract, the butanolic fraction showed activity againstSV-1, acyclovir-resistant strain 29R (EC50 = 2 �g/ml, selec-

ivity index = 8), and the ethyl acetate fraction had a moderateffect on poliovirus type 2. None of the three fractions hadny effect on HSV-1, strain KOS (Andrighetti-Frohner et al.,005).

.1.3. Antiprotozoal activityA methanolic extract of aerial parts showed IC50 val-

es of 58.1 �g/ml on Entamoeba histolytica (moderate) and09.4 �g/ml on Giardia lamblia (weak). The positive controlsere emetin (1.05 and 0.42 �g/ml) and metronidazole (0.04

nd 0.21 �g/ml) (Calzada et al., 2006). The activity againstrichomonas vaginalis was low (IC50 = 227.9 �g/ml; metron-dazole: 0.037 �g/ml) (Calzada et al., 2007). A 95% ethanoleaf extract was one of the five most active (50–100% parasiteuppression on Plasmodium falciparum D-6 clone), out of 37ested species (Antoun et al., 2001).

.2. Effects on the nervous system

.2.1. Neurosedative activityAnother widely investigated aspect was neurosedative activ-

ty. Three essential oils of Lippia alba (55% citral, 10%-myrcene = EO I; 63% citral, 23% limonene = EO II; 55%arvone, 12% limonene = EO III) and some of their majoronstituents (citral, myrcene, limonene) were tested for theirehavioural effects on mice. They all exhibited anxiolyticffects in the elevated plus maze test (100–200 mg/kg, i.p.), andecreased rectal temperature. EO II and EO III and the pure com-
ounds exhibited sedative activities at the same dose range (openeld test, rota-rod test). Citral, myrcene and limonene poten-
iated pentobarbital-induced sleeping time (Vale et al., 1999,002). These results, obtained by intraperitoneal injection, can

p2bp

armacology 116 (2008) 211–222 219

ardly be linked to any traditional mode of administration andhe positive control, diazepam (0.75 mg/kg i.p.), was much morective. The relevance of any conclusion concerning the sedativeroperties of the essential oil of Lippia alba in the context of araditional use is doubtful at the moment.

Tests concerning the sedative activity of Lippia alba werelso performed with polar extracts of Lippia alba. Severalydroethanolic extracts (40, 60 and 80% ethanol; 200 mg/kg,.o.), which contained no detectable amounts of volatile com-ounds were tested on mice. The 80% ethanolic extract dideduce latency to induce sleep and potentiate pentobarbital-nduced sleeping time. The results were similar to those ofiazepam (1 mg/kg, i.p.) on sleep latency, but much weaker onts duration. In the rota-rod test, it also significantly increasedhe number of falls and reduced the time spent on the rotatoryar, when compared with the control group. The rectal tem-erature was not affected in this case and the extracts failed toeduce significantly the number of convulsions and mortalityfter pentylenetetrazole injection. The sedative effect seemed toe related to flavonoid content (Zetola et al., 2002). Recently,fter isolating pure polar compounds from a Lippia alba sam-le from Guadeloupe (France) (Hennebelle et al., 2006b), itas established that its major metabolites had only weak oroderate activities on benzodiazepine and GABAA receptors,

he most actively tested product being luteolin-7-diglucuronideIC50 = 101 and 40 �M, respectively) (the IC50 of diazepam anduscimol were 10.0 and 24.5 nM, respectively) (Hennebelle et

l., 2007).

.2.2. Analgesic and anti-inflammatory activitiesEssential oils and an extract of Lippia alba showed anal-

esic properties. As far as the essential oil is concerned, the twohemotypes used for the tests are citral-limonene and carvone-imonene. Both essential oils (1–2 mg/kg p.o.) inhibited up to0.5% acetic acid-induced writhing in mice (100% inhibitionas obtained for 10 mg/kg meperidine, i.p.). The effect waseaker in the formalin test, as comparable inhibition valuesere reached only with 10 mg/kg p.o. Moreover, the effectas observed mainly during the second (inflammatory) phase,

he first (neurogenic) phase being little affected. The citral-imonene chemotype (50 mg/kg p.o.) was the only essentialil that increased latency time to the stimulus in the hot plateest to the same extent (51.5%) as meperidine (10 mg/kg, i.p.;5.7%). The inhibitory effect of the citral-limonene essential oilas reversed by the opioid antagonist naloxone, suggesting aorphinic action mechanism, whereas the effect of the carvone-

imonene chemotype was not reversed by naloxone. (Viana etl., 1998).

An ethanolic leaf extract (150 mg/kg i.p.) and a chloroformicoot extract (367 mg/kg i.p.) had significant anti-inflammatoryctivities (35.1 and 58.7% decrease of granulocytes countedn exudate, respectively) in the carrageenan-induced air-pouch

odel in mice. In the same test, phenylbutazone (100 mg/kg, i.p.)
rovoked a 70.5% decrease in the granulocyte number (Aguiar,006). Use of the intraperitoneal route does not make it possi-le to suppose any anti-inflammatory properties of traditionalreparations of Lippia alba.

2 hnoph

5

pfiete

5

dd

5

ataa3oo7t2bvLt(drad(Psi(

5

travte2meate

emAdtcpi

6

ea

7

hfircdh(htifiPpwntovotomGamitr((bCii

20 T. Hennebelle et al. / Journal of Et

.3. Cardiovascular activity

Traditional use against hypertension was not confirmed byharmacological experimentation, as a 95% ethanolic extractailed to inhibit KCl- and phenylephrine-induced contractionsn isolated rat aorta rings (Guerrero et al., 2002). An aqueousxtract diminished the cardiac rate without affecting the con-ractile force of isolated rat hearts at a dose of 77 �g/ml (Gazolat al., 2004).

.4. Miscellaneous

Several papers report activities that are unrelated to the tra-itional use of the plant. For the most part, they were assesseduring screenings for specific properties.

.4.1. Antioxidant activityColumbian essential oil samples were used to establish

ntioxidant activities. One, which contained 61% carvone, wasested by the DPPH assay (EC50 = 0.28 kg oil/mmol DPPH)nd TEAC (TAA = 14.4 mmol Trolox/kg oil), with very lowctivities (Puertas-Mejia et al., 2002). Another (51% carvone,3% limonene) inhibited FeSO4-induced linoleic acid per-xydation. Its activity was higher than or similar to thosef positive controls between 5 and 20 g/L, e.g. at 5 g/L,2.0, 55.0 and 55.3% linoleic acid remain, for the essen-ial oil, vitamin E and BHA, respectively (Stashenko et al.,004). The presence of limonene, with conjugated doubleonds, may explain this good activity, compared to the pre-ious paper. Pure products from polar leaf extracts fromippia alba have recently been tested for antioxidant activi-

ies. Phenylethanoids proved to be potent inhibitors of DPPHIC50 = 8.2–15.8 �M). Among the tested flavonoids, luteolin-7-iglucuronide was the only one to reach an IC50 (38.2 �M). Theeference compounds were Trolox (12.5 �M) and chlorogeniccid (20.8 �M). Among the major compounds, luteolin-7-iglucuronide (19), verbascoside (10) and calceolarioside E13) inhibited superoxide radical with higher activities inMA-stimulated neutrophil granulocytes than in a cell-freeystem (hypoxanthine–xanthine oxidase), suggesting an anti-nflammatory effect via the regulation of respiratory burstHennebelle et al., 2007).

.4.2. Cytotoxic activityEighteen extracts made from three parts of the plant (roots,

wigs and leaves) with six different solvents (hexane, chlo-oform, acetone, ethanol, methanol, and water) were testedgainst Hep-2 and NCI-H292 cells. The positive control wasincristine (IC50 = 2.8 and 43.8 ng/ml, respectively). Accordingo the threshold of significance determined by the NCI for crudextracts (IC50 < 30 �g/ml), three extracts were cytotoxic to Hep-cells: chloroformic root extract (11.5 �g/ml), ethanolic andethanolic leaf extracts (8.2 and 14.4 �g/ml, respectively). Five

xtracts were toxic to NCI-H292 cells: chloroformic, acetonicnd ethanolic root extracts (4.6, 16.3 and 11.4 �g/ml, respec-ively), chloroformic twig extract (19.7 �g/ml) and hexanic leafxtract (25.1 �g/ml) (Costa et al., 2004).

etpm

armacology 116 (2008) 211–222

An ethanolic leaf extract and a chloroformic root extractxhibited no cytotoxic activity against HeLa cells in the MTTethod for counting living cells. IC50 were both >30 �g/ml.ntitumoral activity against Sarcoma 180 cells in mice was alsoetermined and the inhibition capacities of both extracts on theumor (47.4 and 29.3%, respectively) were below the 58% level,onsidered by the NCI to be the significance threshold. Theositive control was actinomycin D, which caused 87% tumornhibition at 0.3 mg/kg (Aguiar, 2006).

. Toxicity

Aguiar (2006) determined the oral LD50 of Lippia albaxtracts, the values being 460 mg/kg for an ethanolic leaf extractnd 1466 mg/kg for a chloroformic root extract in mice.

. Ethnopharmacological appraisal

Many traditional uses of Lippia alba (Mill.) N.E. Brownave been reported on. A review of well-conducted surveys con-rms that this species has four main uses: gastrointestinal andespiratory troubles, sleep or anxiety disorders and cardiovas-ular complaints (Table 1). Only one study was dedicated toigestive (antiulcerogenic) properties. It has not been reviewedere because the dose was very high (12.5 g dry plant/kg in rat)Pascual et al., 2001). Only one moderate activity on Entamoebaistolytica, which can cause diarrhea and dysentery, could jus-ify the use of this species in some severe digestive troublesn immunocompetent adults. The traditional use against flu maynd an explanation in an antiviral activity against influenza virus.otential anti-inflammatory properties might play a part in res-iratory ailments (Viana et al., 1998; Aguiar, 2006), but existingorks lack positive controls or the mode of administration doesot correspond to traditional practice. As regards neuroseda-ive activity, existing data on sedative properties of this essentialil, or its major constituents citral, limonene, myrcene, and car-one (Vale et al., 1999, 2002; De Sousa et al., 2007) have beenbtained with high doses (100–200 mg/kg) and by intraperi-oneal injection, so they are of little interest in an assessmentf the plant. The sedative activity of a hydroethanolic extract onice and the effect of luteolin-7-diglucuronide (18) on BZD andABA receptors (Zetola et al., 2002; Hennebelle et al., 2007)

re more convincing. Activities are weak, but some traditionalodes of consumption use considerable amounts of plant. For

nstance, the Creole name twa tass for Lippia alba means thathree cups are drunk before sleep. Usage as an antihypertensiveemedy was not confirmed by experimentation, but verbascoside10) and isoverbascoside (12), potent vasorelaxant compoundsYoshikawa et al., 2006), and glycosides of apigenin and luteolin,oth of which possess vasorelaxing properties (Woodman andhan, 2004), were isolated. This highlights the problem of chem-

cal variability, which is common in plants, but is particularlymportant in Lippia alba (Hennebelle et al., 2006a). Variations in
ssential oil composition and yield (0.1–2.2%) make it necessaryo link biological results to a precise and well-defined sam-le. This has generally been done. Less investigation has beenade of any variation in secondary non-volatile compounds, but

hnoph

dlHipstpe

cetSae

euooAtia(

8

udbudaoabtb

R

A

A

A

A

A

A

A

A

A

B

B

B

B

C

C

C

D

D

D

D

F

F

G

G


ifferences exist in HPLC profiles and isolated compounds, fol-owing the geographical origin of samples (Barbosa et al., 2006a;ennebelle et al., 2006b; Hennebelle, 2006). Thus, differences

n the amount and composition of metabolites may explain sur-rising biological results. This leads us to think that future workshould provide accurate information on the major compoundshat are present in the extract or, at least, on the amount of com-ounds such as phenylethanoids or flavonoids, which are quiteasy to determine.

Additional, precisely and quantitatively ascertained, usesonsist mainly of local applications against wounds, skin dis-ases or pain and may be explained by inhibitory activities ofhe leaf essential oil and extracts on skin pathogens such astaphylococcus aureus, Staphylococcus epidermidis, Candidalbicans or HSV (Aguiar, 2006; Pino Alea et al., 1996; Duartet al., 2005; Andrighetti-Frohner et al., 2005).

A convincing analgesic activity of the essential oil (Vianat al., 1998) may not only play a part in several traditionalses: digestive troubles and respiratory infections, but also inther indications that have been mentioned, such as headachesr gynecological troubles (Scarpa, 2004; Leonti et al., 2003;rango Caro, 2004). It has been reported (although not quanti-

atively) that the plant was used to prepare antimalarial remediesn French Guiana (Vigneron et al., 2005). An interesting activitygainst a chloroquine-resistant clone of Plasmodium falciparumAntoun et al., 2001) should encourage further studies.

. Conclusion

Lippia alba is a popular medicinal plant that is consideredseful in numerous ailments, mainly digestive, respiratory, car-iovascular troubles and anxiety. Various biological studies haveeen dedicated to this species, but a small number of them areseful in evaluating its traditional uses. The sedative activityeserves further investigation, for example clinical trials. Somenti-infectious properties have also been revealed, but the effectsn respiratory pathogens have not been well studied. Digestivend respiratory complaints are important indications and shoulde studied more thoroughly at relevant doses. Special atten-ion should be given to the characterisation of assayed extracts,ecause of their chemical variability.

eferences

bad, M.J., Bermejo, P., Villar, A., Sanchez Palomino, S., Carrasco, L., 1997.Antiviral activity of medicinal plant extracts. Phytotherapy Research 11,198–202.

dams, C.D., 1972. Flowering Plants of Jamaica. University of the West Indies,Glasgow University Press, Glasgow.

guiar, J.S., 2006. Atividades antimicrobiana, citotoxica, antitumoral e antiin-flamatoria de extratos brutos de Lippia alba (Mill.) N.E. Brown. Mestradoem ciencias biologicas, Universidade de Pernambuco.

lanıs, A.D., Calzada, F., Cervantes, J.A., Torres, J., Ceballos, G.M., 2005.Antibacterial properties of some plants used in Mexican traditional medicine
for the treatment of gastrointestinal disorders. Journal of Ethnopharmacol-ogy 100, 153–157.
lbuquerque, U.P., Monteiro, J.M., Ramosa, M.A., Amorim, E.L.C., 2007a.Medicinal and magic plants from a public market in northeastern Brazil.Journal of Ethnopharmacology 110, 76–91.

G

armacology 116 (2008) 211–222 221

lbuquerque, U.P., Medeiros, P.M., Almeida, A.L.S., Monteiro, J.M., Lins Neto,E.M.F., Melo, J.G., Santos, J.P., 2007b. Medicinal plants of the caatinga(semi-arid) vegetation of NE Brazil: a quantitative approach. Journal ofEthnopharmacology 114, 325–354.

ndrighetti-Frohner, C.R., Sincero, T.C.M., da Silva, A.C., Savi, L.A., Gaido,C.M., Bettega, J.M.R., Mancini, M., de Almeida, M.T.R., Barbosa, R.A.,Farias, M.R., Barardi, C.R.M., Simoes, C.M.O., 2005. Antiviral evalua-tion of plants from Brazilian atlantic tropical forest. Fitoterapia 76, 374–378.

ntoun, M.D., Ramos, Z., Vazques, J., Oquendo, I., Proctor, G.R., Gerena, L.,Franzblau, S.G., 2001. Evaluation of the flora of Puerto Rico for in vitroantiplasmodial and antimycobacterial activities. Phytotherapy Research 15,638–642.

rango Caro, S., 2004. Guia de plantas medicinales de uso comun en Salento,Colombia. Missouri Botanical Garden Press, Saint-Louis, pp. 49–50.

arbosa, F.G., Lima, M.A.S., Silveira, E.R., 2005. Total NMR assignments ofnew [C7-OC7]-biflavones from leaves of the limonene-carvone chemotypeof Lippia alba (Mill) N.E. Brown. Magnetic Resonance in Chemistry 43,334–338.

arbosa, F.G., Lima, M.A.S., Braz-Filho, R., Silveira, E.R., 2006a. Iridoid andphenylethanoid glycosides from Lippia alba. Biochemical Systematics andEcology 34, 819–821.

arbosa, F.F., Barbosa, L.C.A., Melho, E.C., Botelho, F.M., Santos, R.H.S.,2006b. Influencia da temperature do ar de secagem sobre o teor e acomposicao quımica do oleo essencial de Lippia alba (Mill) N.E. Brown.Quimica Nova 29, 1221–1225.

orges-Argaez, R., Canche-Chay, C.I., Pena-Rodrıguez, L.M., Said-Fernandez,S., Molina-Salinas, G.M., 2007. Antimicrobial activity of Diospyros anisan-dra. Fitoterapia 78, 370–372.

alzada, F., Yepez-Mulia, L., Aguilar, A., 2006. In vitro susceptibility ofEntamoeba histolytica and Giardia lamblia to plants used in Mexican tra-ditional medicine for the treatment of gastrointestinal disorders. Journal ofEthnopharmacology 108, 367–370.

alzada, F., Yepez-Mulia, L., Tapia-Contreras, A., 2007. Effect of Mexicanmedicinal plant used to treat trichomoniasis on Trichomonas vaginalistrophozoites. Journal of Ethnopharmacology 113, 248–251.

osta, M.C.C.D., Aguiar, J.S., do Nascimiento, S.C., 2004. Atividade citotoxicade extratos brutos de Lippia alba (Mill.) N.E. Brown (Verbenaceae). ActaFarmaceutica Bonaerense 23, 349–352.

ay, M.D., Mc Andrew, T.D., 2003. The biology and host range of Falco-nia intermedia (Hemiptera: Miridae), a potential biological control agentfor Lantana camara (Verbenaceae) in Australia. Biocontrol Science andTechnology 13, 13–22.

e Sousa, D.P., De Farias Nobrega, F.F., De Almeida, R.N., 2007. Influence ofthe chirality of (R)-(−)- and (S)-(+)-carvone in the central nervous system:a comparative study. Chirality 19, 264–268.

i Stasi, L.C., Oliveira, G.P., Carvalhaes, M.A., Queiroz-Junior, M., Tien, O.S.,Kakinami, S.H., Reis, M.S., 2002. Medicinal plants popularly used in theBrazilian Tropical Atlantic Forest. Fitoterapia 73, 69–91.

uarte, M.C.T., Figueira, G.M., Sartoratto, A., Rehder, V.L.G., Delarmelina,C., 2005. Anti-Candida activity of Brazilian medicinal plants. Journal ofEthnopharmacology 97, 305–311.

ournet, J., 2002. Flore Illustree des Phanerogames de Guadeloupe et de Mar-tinique (tome 2). CIRAD, Gondwana Editions, Tartane.

ranco, E.A.P., Barros, R.F.M., 2006. Uso e diversidade de plantas medicinaisno Quilombo Olho D’agua dos Pires, Esperantina Piauı. Revista Brasileirade Plantas Medicinais 8, 68–88.

azola, R., Machado, D., Ruggiero, C., Singi, G., Macedo Alexandre, M., 2004.Lippia alba, Melissa officinalis and Cymbopogon citratus: effects of theaqueous extracts on the isolated hearts of rats. Pharmacological Research50, 477–480.

azzaneo, L.R.S., de Lucena, R.F.P., de Albuquerque, U.P., 2005. Knowledgeand use of medicinal plants by local specialists in a region of Atlantic Forest
in the state of Pernambuco (Northeastern Brazil). Journal of Ethnobiologyand Ethnomedicine 1, 1–8, doi:10.1186/1746-4269-1-9.
iron, L.M., Freire, V., Alonzo, A., Caceres, A., 1991. Ethnobotanical sur-vey of the medicinal flora used by the Caribs of Guatemala. Journal ofEthnopharmacology 34, 173–187.

2 hnoph

G

H

H

H

H

H

H

H

I

I

L

M

O

P

P

P

P

R

R

R

S

S

S

S

S

S

S

S

S

T

V

V

V

V

V

V

V

W

Y

Chemistry 15, 7468–7475.

22 T. Hennebelle et al. / Journal of Et

uerrero, M.F., Puebla, P., Martin, M.L., Arteaga, L., San Roman, L., 2002.Assessment of the antihypertensive and vasodilator effects of ethanolicextracts of some Colombian medicinal plants. Journal of Ethnopharmacol-ogy 80, 37–42.

einrich, M., Rimpler, H., Barrera, N.A., 1992. Indigenous phytotherapy ofgastrointestinal disorders in a lowland Mixe community (Oaxaca, Mexico):ethnopharmacologic evaluation. Journal of Ethnopharmacology 36, 63–80.

ennebelle, T., 2006. Investigation chimique, chimiotaxonomique et pharma-cologique de Lamiales productrices d’antioxydants. Memoire de doctorat,Universite des Sciences et Technologies de Lille.

ennebelle, T., Sahpaz, S., Dermont, C., Joseph, H., Bailleul, F., 2006a. Theessential oil of Lippia alba: analysis of samples from French overseasdepartments and review of previous works. Chemistry and Biodiversity 3,1116–1125.

ennebelle, T., Sahpaz, S., Joseph, H., Bailleul, F., 2006b. Phenolics and iridoidsof Lippia alba. Natural Product Communications 1, 727–730.

ennebelle, T., Sahpaz, S., Gressier, B., Joseph, H., Bailleul, F., 2007. Antiox-idant and neurosedative properties of polyphenols and iridoids from Lippiaalba. Phytotherapy Research 22, 256–258.

oletz, F.B., Pessini, G.L., Sanches, N.R., Cortez, D.A.G., Nakamura, C.V.,Filho, B.P.D., 2002. Screening of some plants used in the brazilian folkmedicine for the treatment of infectious diseases. Memorias do InstitutoOswaldo Cruz 97, 1027–1031.

oward, R.A., 1989. Flora of the Lesser Antilles. Arnold Arboretum, HarvardUniversity, Jamaica Plain, Massachussetts.

PNI (International Plant Names Index). Available at: http://www.ipni.org(accessed in 12 November, 2007).

SB (Institute for Systematic Botany): Atlas of Florida Vascular plants. Availableat: http://www.plantatlas.usf.edu/synonyms.asp?plantID=1589 (accessed in26 August, 2007).

eonti, M., Sticher, O., Heinrich, M., 2003. Antiquity of medicinal plant usage intwo Macro-Mayan ethnic groups (Mexico). Journal of Ethnopharmacology88, 119–124.

atos, F.J.A., Machado, M.I.L., Craveiro, A.A., Alencar, J.W., 1996. Essentialoil composition of two chemotypes of Lippia alba grown in northeast Brazil.Journal of Essential Oil Research 8, 695–698.

liveira, D.R., Leitao, G.G., Santos, S.S., Bizzo, H.R., Lopes, D., Alviano,C.S., Alviano, D.S., Leitao, S.G., 2006. Ethnopharmacological study of twoLippia species from Oriximina, Brazil. Journal of Ethnopharmacology 108,103–108.

ascual, M.E., Slowing, K., Carretero, E., Villar, A., 2001. Antiulcerogenicactivity of Lippia alba (Mill.) N.E. Brown (Verbenaceae). Il Farmaco 56,501–504.

ino Alea, J.A., Ortega Luis, A.G., Rosado Perez, A., Rodrıguez Jorge, M.,Baluja, R., 1996. Composicion y propiedades antibacterianas del aceite esen-cial de Lippia alba (Mill.) N.E. Brown. Revista Cubana de Farmacia 30,0–10.

into, E.P.P., Amorozo, M.C.M., Furlan, A., 2006. Conhecimento popular sobreplantas medicinais em comunidades rurais de mata atlantica—Itacare, BA,Brasil. Acta Botanica Brasilica 20, 751–762.

uertas-Mejia, M., Hillebrand, S., Stashenko, E., Winterhalter, P., 2002. In vitroradical scavenging activity of essential oils from Columbian plants andfractions from oregano (Origanum vulgare L.) essential oil. Flavour andFragrance Journal 17, 380–384.

obard, I., 2003. Plantes medicinales d’outre-mer et pharmacopees: aspectsjuridiques, economiques et culturels. Phytotherapie—De la Recherche a laPratique 1, 16–21.

odrigues, A.C.C., Guedes, M.L.S., 2006. Utilizacao de plantas medicinais noPovoado Sapucaia, Cruz das Almas—Bahia. Revista Brasileira de PlantasMedicinais 8, 1–7.

uffa, M.J., Wagner, M.L., Suriano, M., Vicente, C., Nadinic, J., Pampuro,S., Salomon, H., Campos, R.H., Cavallaro, L., 2004. Inhibitory effect ofmedicinal herbs against RNA and DNA viruses. Antiviral Chemistry and
Chemotherapy 15, 153–159.
astre, C., Breuil, A., 2007. Plantes, milieu et paysages des Antilles francaises.Ecologie, biologie, identification, protection et usages. Biotope, collectionParthenope, Meze.

Z

armacology 116 (2008) 211–222

carpa, G.F., 2004. Medicinal plants used by the Criollos of NorthwesternArgentine Chaco. Journal of Ethnopharmacology 91, 115–135.

ena Filho, J.G., Melo, J.G.S., Saraiva, A.M., Goncalves, A.M., Psiottano,M.N.C., Xavier, H.S., 2006. Antimicrobial activity and phytochemical pro-file from the roots of Lippia alba (Mill.) N.E. Brown. Revista Brasileira deFarmacognosia 16, 506–509.

ena Filho, J.G., Duringer, J.M., Uchoa, D.E.A., Xavier, H.S., Barbosa Filho,J.M., Braz Filho, R., 2007. Distribution of iridoid glycosides in plants fromthe genus Lippia (Verbenaceae): An investigation of Lippia alba (Mill.) N.E.Brown. Natural Product Communications 2, 715–716.

enatore, F., Rigano, D., 2001. Essential oil of two Lippia spp. (Verbenaceae)growing wild in Guatemala. Flavour and Fragrance Journal 16, 169–171.

ilva, N.A., Oliveira, F.F., Costa, L.C.B., Bizzo, H.R., Oliveira, R.A., 2006.Caracterizacao quımica do oleo essencial da erva cidreira (Lippia alba(Mill.) N.E. Br.) cultivada em Ilheus na Bahia. Revista Brasileira de PlantasMedicinais Botucatu 8, 52–55.

ingh, G., Rao, G.P., Kapoor, P.S., Singh, O.P., 2000. Chemical constituents andantifungal activity of Lippia alba Mill. leaf essential oil. Journal of Medicinaland Aromatic Plant Sciences 22, 701–703.

tashenko, E.E., Jaramillo, B.E., Martınez, J.R., 2003. Comparacion de la com-posicion quımica y de la actividad antioxidante in vitro de los metabolitossecundarios volatiles de plantas de la familia Verbenaceae. Revista de laAcademia Colombiana de Ciencias 27, 579–597.

tashenko, E.E., Jaramillo, B.E., Martinez, J.R., 2004. Comparison of differ-ent extraction methods for the analysis of volatile secondary metabolitesof Lippia alba (Mill.) N.E. Brown, grown in Colombia, and evaluation ofits in vitro antioxidant activity. Journal of Chromatography A 1025, 93–103.

oscano-Gonzalez, J.Y., 2006. Uso tradicional de plantas medicinales en lavereda San Isidro, municipio de San Jose de Pare-Boyaca: un estudio pre-liminar usando tecnicas cuantitativas. Acta Biologica Colombiana 11, 137–146.

ale, T.G., Matos, F.J.A., Lima, T.C.M., Viana, G.S.B., 1999. Behavioral effectsof essential oils from Lippia alba (Mill.) N.E. Brown chemotypes. Journalof Ethnopharmacology 167, 127–133.

ale, T.G., Furtado, E.C., Santos Jr., J.G., Viana, G.S.B., 2002. Centraleffects of citral, myrcene and limonene, constituents of essential oilchemotypes from Lippia alba (Mill.) N.E. Brown. Phytomedicine 9, 709–714.

endruscolo, G.S., Mentz, L.A., 2006. Estudo da concordancia das citacoes deuso e importancia das especies e famılias utilizadas como medicinais pelacomunidade do bairro Ponta Grossa, Porto Alegre, RS, Brasil. Acta BotanicaBrasilica 20, 367–382.

erpoorte, R., Houghton, P.J., Heinrich, M., Mukherjee, P.K., SchmedaHirschmann, G., van Staden, J., Yesilada, E., 2006. Editorial. Journal ofEthnopharmacology 103, 309–310.

iana, G.S.B., do Vale, T.G., Rao, V.S.N., Matos, F.J.A., 1998. Analgesic andantiinflammatory effects of two chemotypes of Lippia alba: a comparativestudy. Pharmaceutical Biology 36, 347–351.

igneron, M., Deparis, X., Deharo, E., Bourdy, G., 2005. Antimalarial remediesin French Guiana: a knowledge attitudes and practices study. Journal ofEthnopharmacology 98, 351–360.

on Poser, G.L., Toffoli, M.E., Sobral, M., Henriques, A.T., 1997. Iridoid gluco-sides substitution patterns in Verbenaceae and their taxonomic implication.Plant Systematics and Evolution 205, 265–287.

oodman, O.L., Chan, E.C.H., 2004. Vascular and anti-oxidant actions offlavonols and flavones. Clinical and Experimental Pharmacology and Phys-iology 31, 786–790.

oshikawa, M., Matsuda, H., Morikawa, T., Xie, H., Nakamura, S., Muraoka,O., 2006. Phenylethanoid oligoglycosides and acylated oligosugars withvasorelaxant activity from Cistanche tubulosa. Bioorganic and Medicinal

etola, M., Lima, T.C.M., Sonaglio, D., Gonzalez-Ortega, G., Limberger, R.P.,Petrovick, P.R., Bassani, P.R., 2002. CNS activities of liquid and spray-driedextracts from Lippia alba—Verbenaceae (Brazilian false melissa). Journalof Ethnopharmacology 82, 207–215.

http://www.ipni.org/

http://www.plantatlas.usf.edu/synonyms.asp%3FplantID=1589

review ethnopharmacology of lippia alba lippa - lippia alba/ethnopharm… · available online at...

Documents