title: Physalis angulata induces death of promastigotes and amastigotes of Leishmania (Leishmania) amazonensis via the generation of reactive oxygen species.
abstract: Leishmaniasis are a neglected group of emerging diseases that have been found in 98 countries and are caused by protozoa of the genus Leishmania. The therapy for leishmaniasis causes several side effects and leads to drug-resistant strains. Natural products from plants have exhibited activities against Leishmania in various experimental models. Physalis angulata is a widely used plant in popular medicine, and in the literature it has well-documented leishmanicidal activity. However, its mechanism of action is still unknown. Thus, this study aims to evaluate the mechanism driving the leishmanicidal activity of an aqueous extract of P. angulata root (AEPa). AEPa was effective against both promastigotes and intracellular amastigote forms of Leishmania amazonensis. This effect was mediated by an increase of reactive oxygen species (ROS), but not of nitric oxide (NO). The increased production of ROS induces cell death by phenotypes seems by apoptosis cell death in Leishmania, but not autophagy or necrosis. In addition, morphological analysis of macrophages showed that AEPa induced a high number of cytoplasmic projections, increased the volume of cytoplasm and number of vacuoles, caused cytoskeleton alterations and resulted in high spreading ability. AEPa also promoted superoxide anion (O2(-)) production in both uninfected macrophages and those infected with Leishmania. Therefore, these results revealed that AEPa causes cell death by phenotypes seems by apoptosis cell death in L. amazonensis and modulates macrophage activation through morphofunctional alterations and O2(-) generation to induce Leishmania death.
authors.affiliation: Federal University of Pará, Institute of Biological Sciences, Laboratory of Parasitology and Laboratory of Structural Biology, Belém, Pará, Brazil; National Institute of Science and Technology in Structural Biology and Bioimaging, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: B J M
authors.initials: BJM
authors.lastname: Da Silva
authors.affiliation: Federal University of Pará, Institute of Biological Sciences, Laboratory of Parasitology and Laboratory of Structural Biology, Belém, Pará, Brazil; National Institute of Science and Technology in Structural Biology and Bioimaging, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: R R P
authors.initials: RRP
authors.lastname: Da Silva
authors.affiliation: National Institute of Science and Technology in Structural Biology and Bioimaging, Rio de Janeiro, Rio de Janeiro, Brazil; Evandro Chagas Institute, Laboratory of Electron Microscopy, Department of Health Surveillance, Ministry of Health, Belém, Pará, Brazil.
authors.forename: A P D
authors.initials: APD
authors.lastname: Rodrigues
authors.affiliation: Federal University of Pará, Institute of Biological Sciences, Laboratory of Parasitology and Laboratory of Structural Biology, Belém, Pará, Brazil; National Institute of Science and Technology in Structural Biology and Bioimaging, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: L H S
authors.initials: LHS
authors.lastname: Farias
authors.affiliation: Federal University of Pará, Institute of Biological Sciences, Laboratory of Neurochemistry Molecular and Cellular, Belém, Pará, Brazil.
authors.forename: J L M
authors.initials: JLM
authors.lastname: Do Nascimento
authors.affiliation: Federal University of Pará, Institute of Biological Sciences, Laboratory of Parasitology and Laboratory of Structural Biology, Belém, Pará, Brazil; National Institute of Science and Technology in Structural Biology and Bioimaging, Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: edilene@ufpa.br.
authors.forename: E O
authors.initials: EO
authors.lastname: Silva
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy; D007891:Leishmania / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D008018:Life Cycle Stages / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000469:parasitology / Q000648:ultrastructure; D051379:Mice; D009336:Necrosis / Q000469:parasitology; D032321:Physalis / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D010936:Plant Extracts; D017382:Reactive Oxygen Species
keywords: Antileishmanial activity; L. (L.) amazonensis; Macrophage activation; Physalis angulata; ROS production