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Cytotoxic and Antileishmanial Effects of the Monoterpene β-Ocimene
Leishmaniasis is a group of infectious-parasitic diseases with high mortality rates, and endemic in many regions of the globe. The currently available drugs present serious problems such as high toxicity, costs, and the emergence of drug resistance. This has stimulated research into new antileishman...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960243/ https://www.ncbi.nlm.nih.gov/pubmed/37259336 http://dx.doi.org/10.3390/ph16020183 |
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author | de Sousa, Julyanne Maria Saraiva Nunes, Thaís Amanda de Lima Rodrigues, Raiza Raianne Luz de Sousa, João Paulo Araújo Val, Maria da Conceição Albuquerque Coelho, Francisco Alex da Rocha dos Santos, Airton Lucas Sousa Maciel, Nicolle Barreira de Souza, Vanessa Maria Rodrigues Machado, Yasmim Alves Aires Sousa, Paulo Sérgio de Araújo de Araújo, Alyne Rodrigues Rocha, Jefferson Almeida de Sousa, Damião Pergentino da Silva, Marcos Vinicius Arcanjo, Daniel Dias Rufino Rodrigues, Klinger Antônio da Franca |
author_facet | de Sousa, Julyanne Maria Saraiva Nunes, Thaís Amanda de Lima Rodrigues, Raiza Raianne Luz de Sousa, João Paulo Araújo Val, Maria da Conceição Albuquerque Coelho, Francisco Alex da Rocha dos Santos, Airton Lucas Sousa Maciel, Nicolle Barreira de Souza, Vanessa Maria Rodrigues Machado, Yasmim Alves Aires Sousa, Paulo Sérgio de Araújo de Araújo, Alyne Rodrigues Rocha, Jefferson Almeida de Sousa, Damião Pergentino da Silva, Marcos Vinicius Arcanjo, Daniel Dias Rufino Rodrigues, Klinger Antônio da Franca |
author_sort | de Sousa, Julyanne Maria Saraiva |
collection | PubMed |
description | Leishmaniasis is a group of infectious-parasitic diseases with high mortality rates, and endemic in many regions of the globe. The currently available drugs present serious problems such as high toxicity, costs, and the emergence of drug resistance. This has stimulated research into new antileishmania drugs based on natural products and their derivatives. β-Ocimene is a monoterpene found naturally in the essential oils of many plant species which presents antileishmanial activity, and which has not yet been evaluated for its potential to inhibit the etiological agent of leishmaniasis. The aim of this work was to evaluate the activity of β-ocimene against Leishmania amazonensis, its cytotoxicity, and potential mechanisms of action. β-Ocimene presented direct activity against the parasite, with excellent growth inhibition of promastigotes (IC(50) = 2.78 μM) and axenic amastigotes (EC(50) = 1.12 μM) at concentrations non-toxic to RAW 264.7 macrophages (CC(50) = 114.5 µM). The effect is related to changes in membrane permeability and resulting abnormalities in the parasitic cell shape. These were, respectively, observed in membrane integrity and atomic force microscopy assays. β-Ocimene was also shown to act indirectly, with greater activity against intra-macrophagic amastigotes (EC(50) = 0.89 μM), increasing TNF-α, nitric oxide (NO), and reactive oxygen species (ROS), with lysosomal effects, as well as promoting decreases in IL-10 and IL-6. Against intra-macrophagic amastigote forms the selectivity index was higher than the reference drugs, being 469.52 times more selective than meglumine antimoniate, and 42.88 times more selective than amphotericin B. Our results suggest that β-ocimene possesses promising in vitro antileishmania activity and is a potential candidate for investigation in in vivo assays. |
format | Online Article Text |
id | pubmed-9960243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99602432023-02-26 Cytotoxic and Antileishmanial Effects of the Monoterpene β-Ocimene de Sousa, Julyanne Maria Saraiva Nunes, Thaís Amanda de Lima Rodrigues, Raiza Raianne Luz de Sousa, João Paulo Araújo Val, Maria da Conceição Albuquerque Coelho, Francisco Alex da Rocha dos Santos, Airton Lucas Sousa Maciel, Nicolle Barreira de Souza, Vanessa Maria Rodrigues Machado, Yasmim Alves Aires Sousa, Paulo Sérgio de Araújo de Araújo, Alyne Rodrigues Rocha, Jefferson Almeida de Sousa, Damião Pergentino da Silva, Marcos Vinicius Arcanjo, Daniel Dias Rufino Rodrigues, Klinger Antônio da Franca Pharmaceuticals (Basel) Article Leishmaniasis is a group of infectious-parasitic diseases with high mortality rates, and endemic in many regions of the globe. The currently available drugs present serious problems such as high toxicity, costs, and the emergence of drug resistance. This has stimulated research into new antileishmania drugs based on natural products and their derivatives. β-Ocimene is a monoterpene found naturally in the essential oils of many plant species which presents antileishmanial activity, and which has not yet been evaluated for its potential to inhibit the etiological agent of leishmaniasis. The aim of this work was to evaluate the activity of β-ocimene against Leishmania amazonensis, its cytotoxicity, and potential mechanisms of action. β-Ocimene presented direct activity against the parasite, with excellent growth inhibition of promastigotes (IC(50) = 2.78 μM) and axenic amastigotes (EC(50) = 1.12 μM) at concentrations non-toxic to RAW 264.7 macrophages (CC(50) = 114.5 µM). The effect is related to changes in membrane permeability and resulting abnormalities in the parasitic cell shape. These were, respectively, observed in membrane integrity and atomic force microscopy assays. β-Ocimene was also shown to act indirectly, with greater activity against intra-macrophagic amastigotes (EC(50) = 0.89 μM), increasing TNF-α, nitric oxide (NO), and reactive oxygen species (ROS), with lysosomal effects, as well as promoting decreases in IL-10 and IL-6. Against intra-macrophagic amastigote forms the selectivity index was higher than the reference drugs, being 469.52 times more selective than meglumine antimoniate, and 42.88 times more selective than amphotericin B. Our results suggest that β-ocimene possesses promising in vitro antileishmania activity and is a potential candidate for investigation in in vivo assays. MDPI 2023-01-26 /pmc/articles/PMC9960243/ /pubmed/37259336 http://dx.doi.org/10.3390/ph16020183 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article de Sousa, Julyanne Maria Saraiva Nunes, Thaís Amanda de Lima Rodrigues, Raiza Raianne Luz de Sousa, João Paulo Araújo Val, Maria da Conceição Albuquerque Coelho, Francisco Alex da Rocha dos Santos, Airton Lucas Sousa Maciel, Nicolle Barreira de Souza, Vanessa Maria Rodrigues Machado, Yasmim Alves Aires Sousa, Paulo Sérgio de Araújo de Araújo, Alyne Rodrigues Rocha, Jefferson Almeida de Sousa, Damião Pergentino da Silva, Marcos Vinicius Arcanjo, Daniel Dias Rufino Rodrigues, Klinger Antônio da Franca Cytotoxic and Antileishmanial Effects of the Monoterpene β-Ocimene |
title | Cytotoxic and Antileishmanial Effects of the Monoterpene β-Ocimene |
title_full | Cytotoxic and Antileishmanial Effects of the Monoterpene β-Ocimene |
title_fullStr | Cytotoxic and Antileishmanial Effects of the Monoterpene β-Ocimene |
title_full_unstemmed | Cytotoxic and Antileishmanial Effects of the Monoterpene β-Ocimene |
title_short | Cytotoxic and Antileishmanial Effects of the Monoterpene β-Ocimene |
title_sort | cytotoxic and antileishmanial effects of the monoterpene β-ocimene |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960243/ https://www.ncbi.nlm.nih.gov/pubmed/37259336 http://dx.doi.org/10.3390/ph16020183 |
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