The monoterpene 1,8-cineole prevents cerebral edema in a murine model of severe malaria.
1,8-Cineole is a naturally occurring compound found in essential oils of different plants and has well-known anti-inflammatory and antimicrobial activities. In the present work, we aimed to investigate its potential antimalarial effect, using the following experimental models: (1) the erythrocytic c...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0268347 |
| _version_ | 1818523313936269312 |
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| author | Edgleyson C Dos Santos Leandro S Silva Alessandro S Pinheiro Douglas E Teixeira Diogo B Peruchetti Rodrigo P Silva-Aguiar Camila H C Wendt Kildare R Miranda Andrelina N Coelho-de-Souza José Henrique Leal-Cardoso Celso Caruso-Neves Ana Acacia S Pinheiro |
| author_facet | Edgleyson C Dos Santos Leandro S Silva Alessandro S Pinheiro Douglas E Teixeira Diogo B Peruchetti Rodrigo P Silva-Aguiar Camila H C Wendt Kildare R Miranda Andrelina N Coelho-de-Souza José Henrique Leal-Cardoso Celso Caruso-Neves Ana Acacia S Pinheiro |
| author_sort | Edgleyson C Dos Santos |
| collection | DOAJ |
| description | 1,8-Cineole is a naturally occurring compound found in essential oils of different plants and has well-known anti-inflammatory and antimicrobial activities. In the present work, we aimed to investigate its potential antimalarial effect, using the following experimental models: (1) the erythrocytic cycle of Plasmodium falciparum; (2) an adhesion assay using brain microvascular endothelial cells; and (3) an experimental cerebral malaria animal model induced by Plasmodium berghei ANKA infection in susceptible mice. Using the erythrocytic cycle of Plasmodium falciparum, we characterized the schizonticidal effect of 1,8-cineole. This compound decreased parasitemia in a dose-dependent manner with a half maximal inhibitory concentration of 1045.53 ± 63.30 μM. The inhibitory effect of 972 μM 1,8-cineole was irreversible and independent of parasitemia. Moreover, 1,8-cineole reduced the progression of intracellular development of the parasite over 2 cycles, inducing important morphological changes. Ultrastructure analysis revealed a massive loss of integrity of endomembranes and hemozoin crystals in infected erythrocytes treated with 1,8-cineole. The monoterpene reduced the adhesion index of infected erythrocytes to brain microvascular endothelial cells by 60%. Using the experimental cerebral malaria model, treatment of infected mice for 6 consecutive days with 100 mg/kg/day 1,8-cineole reduced cerebral edema with a 50% reduction in parasitemia. Our data suggest a potential antimalarial effect of 1,8-cineole with an impact on the parasite erythrocytic cycle and severe disease. |
| first_indexed | 2024-12-11T05:43:29Z |
| format | Article |
| id | doaj.art-a595d7bad5d945e7bafd3a097bd1e6ce |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T05:43:29Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a595d7bad5d945e7bafd3a097bd1e6ce2022-12-22T01:19:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01175e026834710.1371/journal.pone.0268347The monoterpene 1,8-cineole prevents cerebral edema in a murine model of severe malaria.Edgleyson C Dos SantosLeandro S SilvaAlessandro S PinheiroDouglas E TeixeiraDiogo B PeruchettiRodrigo P Silva-AguiarCamila H C WendtKildare R MirandaAndrelina N Coelho-de-SouzaJosé Henrique Leal-CardosoCelso Caruso-NevesAna Acacia S Pinheiro1,8-Cineole is a naturally occurring compound found in essential oils of different plants and has well-known anti-inflammatory and antimicrobial activities. In the present work, we aimed to investigate its potential antimalarial effect, using the following experimental models: (1) the erythrocytic cycle of Plasmodium falciparum; (2) an adhesion assay using brain microvascular endothelial cells; and (3) an experimental cerebral malaria animal model induced by Plasmodium berghei ANKA infection in susceptible mice. Using the erythrocytic cycle of Plasmodium falciparum, we characterized the schizonticidal effect of 1,8-cineole. This compound decreased parasitemia in a dose-dependent manner with a half maximal inhibitory concentration of 1045.53 ± 63.30 μM. The inhibitory effect of 972 μM 1,8-cineole was irreversible and independent of parasitemia. Moreover, 1,8-cineole reduced the progression of intracellular development of the parasite over 2 cycles, inducing important morphological changes. Ultrastructure analysis revealed a massive loss of integrity of endomembranes and hemozoin crystals in infected erythrocytes treated with 1,8-cineole. The monoterpene reduced the adhesion index of infected erythrocytes to brain microvascular endothelial cells by 60%. Using the experimental cerebral malaria model, treatment of infected mice for 6 consecutive days with 100 mg/kg/day 1,8-cineole reduced cerebral edema with a 50% reduction in parasitemia. Our data suggest a potential antimalarial effect of 1,8-cineole with an impact on the parasite erythrocytic cycle and severe disease.https://doi.org/10.1371/journal.pone.0268347 |
| spellingShingle | Edgleyson C Dos Santos Leandro S Silva Alessandro S Pinheiro Douglas E Teixeira Diogo B Peruchetti Rodrigo P Silva-Aguiar Camila H C Wendt Kildare R Miranda Andrelina N Coelho-de-Souza José Henrique Leal-Cardoso Celso Caruso-Neves Ana Acacia S Pinheiro The monoterpene 1,8-cineole prevents cerebral edema in a murine model of severe malaria. PLoS ONE |
| title | The monoterpene 1,8-cineole prevents cerebral edema in a murine model of severe malaria. |
| title_full | The monoterpene 1,8-cineole prevents cerebral edema in a murine model of severe malaria. |
| title_fullStr | The monoterpene 1,8-cineole prevents cerebral edema in a murine model of severe malaria. |
| title_full_unstemmed | The monoterpene 1,8-cineole prevents cerebral edema in a murine model of severe malaria. |
| title_short | The monoterpene 1,8-cineole prevents cerebral edema in a murine model of severe malaria. |
| title_sort | monoterpene 1 8 cineole prevents cerebral edema in a murine model of severe malaria |
| url | https://doi.org/10.1371/journal.pone.0268347 |
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