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Ethnopharmacology of Lippia Alba Thierry Hennebelle A, Sevser Sahpaz A, Henry Joseph B, Franc¸Ois Bailleul A,∗ a Laboratoire De Pharmacognosie, E.A

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Ethnopharmacology of Lippia Alba Thierry Hennebelle A, Sevser Sahpaz A, Henry Joseph B, Franc¸Ois Bailleul A,∗ a Laboratoire De Pharmacognosie, E.A 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, Franc¸ois Bailleul a,∗ a Laboratoire de Pharmacognosie, E.A. 1043, Universit´e de Lille 2, Facult´e 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 2007 Available online 8 December 2007 Abstract Introduction: Chemical, ethnopharmacological and pharmacological research on Lippia alba (Mill.) N.E. Brown and the evidence that exists for its various usages have been looked for, focusing on high quality studies. Ethnopharmacological investigation: The species is mainly used against digestive and respiratory ailments, and as a sedative and antihypertensive remedy. Chemical constituents: Seven chemotypes exist for the essential oil, the non-volatile compounds are iridioids, phenylethanoids, flavone glycosides and biflavonoids. Biological activities and ethnopharmacological appraisal: Some positive, although partial, results have been obtained on sedative and anxiolytic activities. Real effects in other traditional uses can mainly be explained by anti-infectious and analgesic properties, at the moment. Conclusion: Well conducted biological studies are still needed for several indications of this species. Its use as a sedative deserves a clinical investigation. The chemical variability of the species seems important both in the essential oil and in non-volatile compounds, so future research on the pharmacological properties of these extracts should provide more chemical data which will increase their validity. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Lippia alba; Verbenaceae; Digestive; Respiratory; Sedative; Hypertension; Anti-infectious Contents 1. Introduction ............................................................................................................ 212 2. Botanical data .......................................................................................................... 212 3. Ethnopharmacological investigation ....................................................................................... 213 4. Chemical constituents ................................................................................................... 213 5. Biological investigation .................................................................................................. 214 5.1. Anti-infectious properties .......................................................................................... 215 5.1.1. Antibacterial and antifungal activity ........................................................................ 215 5.1.2. Antiviral activity .......................................................................................... 219 5.1.3. Antiprotozoal activity ..................................................................................... 219 5.2. Effects on the nervous system ...................................................................................... 219 5.2.1. Neurosedative activity ..................................................................................... 219 5.2.2. Analgesic and anti-inflammatory activities................................................................... 219 Abbreviations: AFSSaPS, Agence Franc¸aise pour la Securit´ e´ Sanitaire des Produits de Sante;´ BHA, butyl-hydroxyanisole; BVDV, bovine viral diarrhoea virus; DPPH, 1,1-diphenyl-2-picrylhydrazyl; EC50, effective concentration 50%; HIV, human immunodeficiency virus; HSV, herpes simplex virus; IC50, inhibiting concentration 50%; LD50, lethal dose 50%; MIC, minimal inhibitory concentration; LSU, level of significative use; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; NCI, National Cancer Institute; PMA, phorbol myristate acetate; TEAC, trolox equivalent antioxidant capacity; TRAMIL, TRAditional Medicine for the IsLands; VSV, vesicular stomatitis virus. ∗ Corresponding author. Tel.: +33 320 964039; fax: +33 320 964039. E-mail address: [email protected] (F. Bailleul). 0378-8741/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2007.11.044 212 T. Hennebelle et al. / Journal of Ethnopharmacology 116 (2008) 211–222 5.3. Cardiovascular activity ............................................................................................ 220 5.4. Miscellaneous .................................................................................................... 220 5.4.1. Antioxidant activity ....................................................................................... 220 5.4.2. Cytotoxic activity ......................................................................................... 220 6. Toxicity ................................................................................................................ 220 7. Ethnopharmacological appraisal .......................................................................................... 220 8. Conclusion ............................................................................................................. 221 References ............................................................................................................. 221 1. Introduction It is a shrub, with a quadrangular branch, reaching 1.7 m in height. The leaves are membranaceous, petiolate, pubescent, Lippia alba (Mill.) N.E. Brown is an aromatic shrub belong- opposite or ternate, and its limb shows variable forms with a ing to the Verbenaceae family, which is widely used all over pointed apex, cuneiform or decumbent basis and serrated or South and Central America for different purposes. In particu- crenated border (except on the basis). The flowers (3–5 mm) are lar, Lippia alba has been used for centuries in French overseas white or pink. The fruit is composed of two indehiscent nucleus, departments (French Guiana, Guadeloupe, Martinique) despite each containing one brown seed (Adams, 1972; Fournet, 2002; the fact that, when slavery was still authorised in France (that is Howard, 1989). to say until 1848), black slaves did not have the right to use or An incredible number of synonyms are to be found for Lip- sell medicinal plants, lest they poisoned white settlers. As the pia alba. They belong to the genera Lippia, Lantana, Phyla, French Pharmacopeia was created during the slavery period, no Verbena and Zapania (ISB, 2007). The explanation may lie in medicinal plants from the overseas departments were included at the variability of the species and more generally in the com- that time, except for those used by white people. In spite of the plexities inherent in the Verbenaceae family. Seven infraspecific abolition of slavery, traditional remedies of black populations taxa of the species Lippia alba (Mill.) N.E. Brown have been had no official status until very recently. Lippia alba and Senna established: Lippia alba f. alba Moldenke, Lippia alba f. inter- alata (L.) Roxb. (Fabaceae) were the first two plants from over- seas departments to be approved by the French Drug Agency (AFSSaPS) for inclusion in the French Pharmacopeia (Robard, 2003). This work is also of interest because of the impending inscription of Lippia alba in European (French and Spanish) Pharmacopeias. The aim of this work is to list and compare papers that have dealt with ethnopharmacological, biological and pharmacological studies of this species, so as to synthesise existing scientific evidence on the different uses of this plant. A discussion of the available data on activities and chemical composition ensues. 2. Botanical data Lippia alba (Mill.) N.E. Brown (Fig. 1) belongs to the Verbe- naceae family, which also includes other medicinally important plants like Aloysia triphylla (L’Herit.)´ Britt. and Verbena offic- inalis L. Lippia alba is abundantly present between the south of the United States of America (Florida) and the north of Argentina. It is also present in India (Singh et al., 2000) and Australia (Day and Mc Andrew, 2003). The local and traditional names are numerous in Latin America, because of widespread traditional use, and are generally derived from its aromatic smell or medicinal properties. The most common name in Brazil is cidreira, but this can also be used for 17 other lemon-scented herbs with similar uses (Matos et al., 1996). In Spanish-speaking countries and French overseas departments, it is often named after other aromatic species, e.g.: salvia morada (Senatore and Rigano, 2001), or´egano de cerro (Stashenko et al., 2003), an´ıs de Espa˜na (Pino Alea et al., 1996), mirto (Alan´ıs et al., 2005), verveine blanche, sauge du Br´esil (Sastre and Breuil, 2007). Fig. 1. Lippia alba (Mill.) N.E. Brown (Verbenaceae) (photograph by H.J.). T. Hennebelle et al. / Journal of Ethnopharmacology 116 (2008) 211–222 213 media Moldenke, Lippia alba f. macrophylla Moldenke, Lippia One survey was specifically dedicated to the species Lippia alba f. scabra Moldenke, Lippia alba var. globiflora (L’Her.)´ alba. Near Oriximina´ (state of Para,´ Brazil), people use two Moldenke, Lippia alba var. carterae Moldenke and Lippia alba different infraspecific taxa of Lippia alba: Lippia alba f. alba var. lanceolata (Griseb.) Mulgura´ (IPNI, 2007). Moldenke (erva-cidreira), which is cultivated, and Lippia alba f. intermedia Moldenke (carmelitana),
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