title: The effect of the phytol-rich fraction from Lacistema pubescens against Leishmania amazonensis is mediated by mitochondrial dysfunction.
abstract: Leishmaniasis is a complex disease caused by protozoan parasite Leishmania and the treatment remains a serious problem since the available drugs exhibited high toxicity and side effects. Plant-derived natural products are promising leads for the development of novel chemotherapeutics. In this work the phytol-rich hexane fraction (PRF) from the leaves of Lacistema pubescens was obtained and identified by GC-MS analysis. When assayed for antileishmanial effects, PRF was active against promastigote and amastigote forms of Leishmania amazonensis (IC50 values of 44.0 and 25.8 μg/mL respectively). Furthermore, PRF did not show significant cytotoxicity on peritoneal macrophages being more destructive to the intracellular parasite than to mammalian cells. In addition, possible targets of PRF were investigated against L. amazonensis promastigotes. The results showed that PRF exerted its antipromastigote activity by marked depolarization of the mitochondrial membrane potential followed by the increase of ROS levels in L. amazonensis promastigotes. During these events, no rupture of the cell membrane integrity was observed. Our results indicated that PRF was effective and selective against L. amazonensis, and that this effect was mainly mediated by mitochondrial dysfunction associated to ROS production.
authors.affiliation: Bioactive Natural Products Laboratory, Department of Biochemistry, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz de Fora, MG Brazil.
authors.forename: Josiane Mello
authors.initials: JM
authors.lastname: da Silva
authors.affiliation: Department of Parasitology, Microbiology and Immunology, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz de Fora, MG Brazil.
authors.forename: Luciana Maria Ribeiro
authors.initials: LM
authors.lastname: Antinarelli
authors.affiliation: Bioactive Natural Products Laboratory, Department of Biochemistry, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz de Fora, MG Brazil.
authors.forename: Antônia
authors.initials: A
authors.lastname: Ribeiro
authors.affiliation: Department of Parasitology, Microbiology and Immunology, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz de Fora, MG Brazil.
authors.forename: Elaine Soares
authors.initials: ES
authors.lastname: Coimbra
authors.affiliation: Bioactive Natural Products Laboratory, Department of Biochemistry, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz de Fora, MG Brazil. Electronic address: elita.scio@ufjf.edu.br.
authors.forename: Elita
authors.initials: E
authors.lastname: Scio
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D020128:Inhibitory Concentration 50; D007894:Leishmania mexicana / Q000187:drug effects* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D019684:Magnoliopsida / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010836:Phytol / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D017382:Reactive Oxygen Species; D010836:Phytol
keywords: Antileishmanial activity; Lacistema pubescens; Leishmania amazonensis; Mitochondrial dysfunction; Phytol