| Author | Rizk, Yasmin Silva | |
| Author | Hardoim, Daiana de Jesus | |
| Author | Santos, Kaique Bertrand Almeida | |
| Author | Valle, Tânia Zaverucha do | |
| Author | Taniwaki, Noemi Nosomi | |
| Author | Souza, Fernando Almeida | |
| Author | Carollo, Carlos Alexandre | |
| Author | Santos, Marcos André Vannier | |
| Author | Arruda, Carla Cardozo Pinto de | |
| Author | Calabrese, Kátia da Silva | |
| Access date | 2022-01-27T18:14:42Z | |
| Available date | 2022-01-27T18:14:42Z | |
| Document date | 2022 | |
| Citation | RIZK, Yasmin Silva et al. Amentoflavone isolated from Selaginella sellowii Hieron induces mitochondrial dysfunction in Leishmania amazonensis promastigotes. Parasitology International, v. 86, 102458, p. 1 - 9, Sept. 2021. | pt_BR |
| ISSN | 1383-5769 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/50920 | |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Biflavonóide | pt_BR |
| Subject in Portuguese | Atividade antileishmania | pt_BR |
| Subject in Portuguese | Mitocôndria | pt_BR |
| Subject in Portuguese | Morte celular | pt_BR |
| Subject in Portuguese | Microscópio eletrônico | pt_BR |
| Title | Amentoflavone isolated from Selaginella sellowii Hieron induces mitochondrial dysfunction in Leishmania amazonensis promastigotes | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.parint.2021.102458 | |
| Abstract | Leishmaniasis chemotherapy is a bottleneck in disease treatment. Although available, chemotherapy is limited,
toxic, painful, and does not lead to parasite clearance, with parasite resistance also being reported. Therefore,
new therapeutic options are being investigated, such as plant-derived anti-parasitic compounds. Amentoflavone
is the most common biflavonoid in the Selaginella genus, and its antileishmanial activity has already been
described on Leishmania amazonensis intracellular amastigotes but its direct action on the parasite is controversial.
In this work we demonstrate that amentoflavone is active on L. amazonensis promastigotes (IC50 = 28.5
± 2.0 μM) and amastigotes. Transmission electron microscopy of amentoflavone-treated promastigotes showed
myelin-like figures, autophagosomes as well as enlarged mitochondria. Treated parasites also presented multiple
lipid droplets and altered basal body organization. Similarly, intracellular amastigotes presented swollen mitochondria,
membrane fragments in the lumen of the flagellar pocket as well as autophagic vacuoles. Flow cytometric
analysis after TMRE staining showed that amentoflavone strongly decreased mitochondrial membrane
potential. In silico analysis shows that amentoflavone physic-chemical, drug-likeness and bioavailability characteristics
suggest it might be suitable for oral administration. We concluded that amentoflavone presents a
direct effect on L. amazonensis parasites, causing mitochondrial dysfunction and parasite killing. Therefore, all
results point for the potential of amentoflavone as a promising candidate for conducting advanced studies for the
development of drugs against leishmaniasis. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Instituto Adolfo Lutz. Núcleo de Microscopia Eletrônica. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e ProtozoRIZK, ologia. Rio de Janeiro, RJ, Brasil / Universidade Estadual do Maranhão. Pós-graduação em Ciência Animal. São Luís, MA, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Mato Grosso do Sul. Instituto de Biociências. Laboratório de Produtos Naturais e Espectrometria de Massas. Campo Grande, MS, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Mato Grosso do Sul. Instituto de Biociências. Laboratório de Parasitologia Humana. Campo Grande, MS, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Biflavonoid | pt_BR |
| Subject | Antileishmanial activity | pt_BR |
| Subject | Mitochondria | pt_BR |
| Subject | Cell death | pt_BR |
| Subject | ADME | pt_BR |
| Subject | Electron microscopy | pt_BR |
| Embargo date | 2024 | |
