TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in <i>Trypanosoma cruzi</i>
Chagas disease is a neglected tropical disease that is caused by the protozoan <i>Trypanosoma cruzi</i> and represents a serious health problem, especially in Latin America. The clinical treatment of Chagas disease is based on two nitroderivatives that present severe side effects and imp...
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MDPI AG
2018-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/23/11/2800 |
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| author | Ana Cristina Souza Bombaça Daniela Von Dossow Juliana Magalhães Chaves Barbosa Cristian Paz Viviana Burgos Rubem Figueiredo Sadok Menna-Barreto |
| author_facet | Ana Cristina Souza Bombaça Daniela Von Dossow Juliana Magalhães Chaves Barbosa Cristian Paz Viviana Burgos Rubem Figueiredo Sadok Menna-Barreto |
| author_sort | Ana Cristina Souza Bombaça |
| collection | DOAJ |
| description | Chagas disease is a neglected tropical disease that is caused by the protozoan <i>Trypanosoma cruzi</i> and represents a serious health problem, especially in Latin America. The clinical treatment of Chagas disease is based on two nitroderivatives that present severe side effects and important limitations. In folk medicine, natural products, including sesquiterpenoids, have been employed for the treatment of different parasitic diseases. In this study, the trypanocidal activity of compounds isolated from the Chilean plants <i>Drimys winteri</i>, <i>Podanthus mitiqui</i> and <i>Maytenus boaria</i> on three <i>T. cruzi</i> evolutive forms (epimastigote, trypomastigote and amastigote) was evaluated. Total extracts and seven isolated sesquiterpenoids were assayed on trypomastigotes and epimastigotes. Polygodial (Pgd) from <i>D. winteri</i>, total extract from <i>P. mitiqui</i> (PmTE) and the germacrane erioflorin (Efr) from <i>P. mitiqui</i> were the most bioactive substances. Pgd, Efr and PmTE also presented strong effects on intracellular amastigotes and low host toxicity. Many ultrastructural effects of these substances, including reservosome disruption, cytosolic vacuolization, autophagic phenotype and mitochondrial swelling (in the case of Pgd), were observed. Flow cytometric analysis demonstrated a reduction in mitochondrial membrane potential in treated epimastigotes and an increase in ROS production and high plasma membrane permeability after treatment with Pgd. The promising trypanocidal activity of these natural sesquiterpenoids may be a good starting point for the development of alternative treatmentsforChagas disease. |
| first_indexed | 2024-12-10T05:41:55Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-10T05:41:55Z |
| publishDate | 2018-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-086a705d96464bc98394bfeca0938a3d2022-12-22T02:00:16ZengMDPI AGMolecules1420-30492018-10-012311280010.3390/molecules23112800molecules23112800TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in <i>Trypanosoma cruzi</i>Ana Cristina Souza Bombaça0Daniela Von Dossow1Juliana Magalhães Chaves Barbosa2Cristian Paz3Viviana Burgos4Rubem Figueiredo Sadok Menna-Barreto5Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, BrazilDepartamento de Ciencias Químicas y Recursos Naturales, Universidad de La Frontera, Temuco 4811230, ChileLaboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, BrazilDepartamento de Ciencias Químicas y Recursos Naturales, Universidad de La Frontera, Temuco 4811230, ChileDepartamento de Ciencias Químicas y Recursos Naturales, Universidad de La Frontera, Temuco 4811230, ChileLaboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, BrazilChagas disease is a neglected tropical disease that is caused by the protozoan <i>Trypanosoma cruzi</i> and represents a serious health problem, especially in Latin America. The clinical treatment of Chagas disease is based on two nitroderivatives that present severe side effects and important limitations. In folk medicine, natural products, including sesquiterpenoids, have been employed for the treatment of different parasitic diseases. In this study, the trypanocidal activity of compounds isolated from the Chilean plants <i>Drimys winteri</i>, <i>Podanthus mitiqui</i> and <i>Maytenus boaria</i> on three <i>T. cruzi</i> evolutive forms (epimastigote, trypomastigote and amastigote) was evaluated. Total extracts and seven isolated sesquiterpenoids were assayed on trypomastigotes and epimastigotes. Polygodial (Pgd) from <i>D. winteri</i>, total extract from <i>P. mitiqui</i> (PmTE) and the germacrane erioflorin (Efr) from <i>P. mitiqui</i> were the most bioactive substances. Pgd, Efr and PmTE also presented strong effects on intracellular amastigotes and low host toxicity. Many ultrastructural effects of these substances, including reservosome disruption, cytosolic vacuolization, autophagic phenotype and mitochondrial swelling (in the case of Pgd), were observed. Flow cytometric analysis demonstrated a reduction in mitochondrial membrane potential in treated epimastigotes and an increase in ROS production and high plasma membrane permeability after treatment with Pgd. The promising trypanocidal activity of these natural sesquiterpenoids may be a good starting point for the development of alternative treatmentsforChagas disease.https://www.mdpi.com/1420-3049/23/11/2800<i>Trypanosoma cruzi</i>chagas diseasechemotherapysesquiterpenoidsmitochondriaautophagy |
| spellingShingle | Ana Cristina Souza Bombaça Daniela Von Dossow Juliana Magalhães Chaves Barbosa Cristian Paz Viviana Burgos Rubem Figueiredo Sadok Menna-Barreto TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in <i>Trypanosoma cruzi</i> Molecules <i>Trypanosoma cruzi</i> chagas disease chemotherapy sesquiterpenoids mitochondria autophagy |
| title | TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in <i>Trypanosoma cruzi</i> |
| title_full | TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in <i>Trypanosoma cruzi</i> |
| title_fullStr | TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in <i>Trypanosoma cruzi</i> |
| title_full_unstemmed | TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in <i>Trypanosoma cruzi</i> |
| title_short | TrypanocidalActivity of Natural Sesquiterpenoids Involves Mitochondrial Dysfunction, ROS Production and Autophagic Phenotype in <i>Trypanosoma cruzi</i> |
| title_sort | trypanocidalactivity of natural sesquiterpenoids involves mitochondrial dysfunction ros production and autophagic phenotype in i trypanosoma cruzi i |
| topic | <i>Trypanosoma cruzi</i> chagas disease chemotherapy sesquiterpenoids mitochondria autophagy |
| url | https://www.mdpi.com/1420-3049/23/11/2800 |
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