title: In vitro effects of triterpenic acids from olive leaf extracts on the mitochondrial membrane potential of promastigote stage of Leishmania spp.
abstract: Protozoan diseases, such as leishmaniasis, are a cause of considerable morbidity throughout the world, affecting millions every year. In this study, two triterpenic acids (maslinic and oleanolic acids) were isolated from Tunisian olive leaf extracts and their in vitro activity against the promastigotes stage of Leishmania (L.) infantum and Leishmania (L.) amazonensis was investigated. Maslinic acid showed the highest activity with an IC50 of 9.32 ± 1.654 and 12.460 ± 1.25 μg/ml against L. infantum and L. amazonensis, respectively. The mechanism of action of these drugs was investigated by detecting changes in the phosphatidylserine (PS) exposure, the plasma membrane permeability, the mitochondrial membrane potential and the ATP level production in the treated parasites. By using the fluorescent probe SYTOX® Green, both triterpenic acids showed that they produce a time-dependent plasma membrane permeabilization in the treated Leishmania species. In addition, spectrofluorimeteric data revealed the surface exposure of PS in promastigotes. Both molecules reduced the mitochondrial membrane potential and decreased the ATP levels to 15% in parasites treated with IC90 for 24h. We conclude that the triterpenic acids tested in this study, show potential as future therapeutic alternative against leishmaniasis. Further studies are needed to confirm this.
authors.affiliation: Laboratoire Matériaux-Molécules et Applications, IPEST, University of Carthage, B.P 51, 2070 La Marsa, Tunisia. Electronic address: ines.sifaoui@hotmail.com.
authors.forename: Ines
authors.initials: I
authors.lastname: Sifaoui
authors.affiliation: University Institute of Tropical Diseases and Public Health, University of La Laguna, Avda Francisco Sanchez s/n, Campus de Anchieta, 38271 La Laguna Tenerife, Canary Islands, Spain.
authors.forename: Atteneri
authors.initials: A
authors.lastname: López-Arencibia
authors.affiliation: University Institute of Tropical Diseases and Public Health, University of La Laguna, Avda Francisco Sanchez s/n, Campus de Anchieta, 38271 La Laguna Tenerife, Canary Islands, Spain.
authors.forename: Carmen Maria
authors.initials: CM
authors.lastname: Martín-Navarro
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González, University of La Laguna, Tenerife, Canary Islands, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Ticona
authors.affiliation: University Institute of Tropical Diseases and Public Health, University of La Laguna, Avda Francisco Sanchez s/n, Campus de Anchieta, 38271 La Laguna Tenerife, Canary Islands, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Reyes-Batlle
authors.affiliation: Laboratoire Matériaux-Molécules et Applications, IPEST, University of Carthage, B.P 51, 2070 La Marsa, Tunisia.
authors.forename: Mondher
authors.initials: M
authors.lastname: Mejri
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González, University of La Laguna, Tenerife, Canary Islands, Spain.
authors.forename: Antonio Ignacio
authors.initials: AI
authors.lastname: Jiménez
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González, University of La Laguna, Tenerife, Canary Islands, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Lopez-Bazzocchi
authors.affiliation: University Institute of Tropical Diseases and Public Health, University of La Laguna, Avda Francisco Sanchez s/n, Campus de Anchieta, 38271 La Laguna Tenerife, Canary Islands, Spain.
authors.forename: Basilio
authors.initials: B
authors.lastname: Valladares
authors.affiliation: University Institute of Tropical Diseases and Public Health, University of La Laguna, Avda Francisco Sanchez s/n, Campus de Anchieta, 38271 La Laguna Tenerife, Canary Islands, Spain.
authors.forename: Jacob
authors.initials: J
authors.lastname: Lorenzo-Morales
authors.affiliation: Laboratoire Matériaux-Molécules et Applications, IPEST, University of Carthage, B.P 51, 2070 La Marsa, Tunisia.
authors.forename: Manef
authors.initials: M
authors.lastname: Abderabba
authors.affiliation: University Institute of Tropical Diseases and Public Health, University of La Laguna, Avda Francisco Sanchez s/n, Campus de Anchieta, 38271 La Laguna Tenerife, Canary Islands, Spain.
authors.forename: José E
authors.initials: JE
authors.lastname: Piñero
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000981:Antiprotozoal Agents / Q000494:pharmacology; D002463:Cell Membrane Permeability; D007891:Leishmania / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D015394:Molecular Structure; D031658:Olea / Q000737:chemistry*; D009828:Oleanolic Acid / Q000494:pharmacology* / Q000031:analogs & derivatives; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D014315:Triterpenes / Q000494:pharmacology
chemical_list: D000981:Antiprotozoal Agents; D010936:Plant Extracts; D014315:Triterpenes; D009828:Oleanolic Acid; D000255:Adenosine Triphosphate; C412811:maslinic acid
keywords: Bioassay fractionation; Chemotherapy; Leishmania spp; Mechanism of action; Olive leaf extract