Impact on parasitemia, survival time and pro-inflammatory immune response in mice infected with Plasmodium berghei treated with Eleutherine plicata
In vitro studies with Plasmodium falciparum have demonstrated the antiparasitic activity of E. plicata, attributed to its naphthoquinones. This study reports on pro-inflammatory changes in mice infected with P. berghei and correlates these changes with parasitemia and survival. The ethanol extract o...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1484934/full |
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| author | Antônio Rafael Quadros Gomes Antônio Rafael Quadros Gomes Ana Laura Gadelha Castro Ana Laura Gadelha Castro Gleison Gonçalves Ferreira Heliton Patrick Cordovil Brígido Everton Luiz Pompeu Varela Everton Luiz Pompeu Varela Valdicley Vieira Vale Liliane Almeida Carneiro Maria Fâni Dolabela Maria Fâni Dolabela Maria Fâni Dolabela Sandro Percario Sandro Percario |
| author_facet | Antônio Rafael Quadros Gomes Antônio Rafael Quadros Gomes Ana Laura Gadelha Castro Ana Laura Gadelha Castro Gleison Gonçalves Ferreira Heliton Patrick Cordovil Brígido Everton Luiz Pompeu Varela Everton Luiz Pompeu Varela Valdicley Vieira Vale Liliane Almeida Carneiro Maria Fâni Dolabela Maria Fâni Dolabela Maria Fâni Dolabela Sandro Percario Sandro Percario |
| author_sort | Antônio Rafael Quadros Gomes |
| collection | DOAJ |
| description | In vitro studies with Plasmodium falciparum have demonstrated the antiparasitic activity of E. plicata, attributed to its naphthoquinones. This study reports on pro-inflammatory changes in mice infected with P. berghei and correlates these changes with parasitemia and survival. The ethanol extract of Eleutherine plicata (EEEp) was fractionated under reflux to obtain the dichloromethane fraction (FDMEp) and isolated compounds from E. plicata, relating these to survival time and parasitemia. Antimalarial activity was evaluated using the Peters suppressive test, with mice infected with Plasmodium berghei and treated with E. plicata, assessing parasitemia and survival over 30 days. The pro-inflammatory profile was determined by measuring interleukin-10, interferon-γ (IFN-γ), and nitric oxide levels. EEEp, FDMEp, and eleutherol showed activity on the 5th day of infection, with only FDMEp being active on the 8th day. Treatment with EEEp and FDMEp extended animal survival, reduced IFN-γ and NO levels, and increased IL-10 levels. Eleutherol significantly altered the response, with eleutherol glucuronide seemingly active by binding to lactate dehydrogenase, inhibiting hemozoin metabolism, leading to parasite death. Pro-inflammatory changes did not appear to correlate with survival and reduced parasitemia. In summary, FDMEp and eleutherol reduced parasitemia, extended survival, and modulated the inflammatory response. FDMEp and eleutherol are promising candidates for developing new antimalarial drugs. |
| format | Article |
| id | doaj-art-449d64e562a549b285b7ea511d854186 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-449d64e562a549b285b7ea511d8541862024-12-05T09:31:30ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-12-011510.3389/fphar.2024.14849341484934Impact on parasitemia, survival time and pro-inflammatory immune response in mice infected with Plasmodium berghei treated with Eleutherine plicataAntônio Rafael Quadros Gomes0Antônio Rafael Quadros Gomes1Ana Laura Gadelha Castro2Ana Laura Gadelha Castro3Gleison Gonçalves Ferreira4Heliton Patrick Cordovil Brígido5Everton Luiz Pompeu Varela6Everton Luiz Pompeu Varela7Valdicley Vieira Vale8Liliane Almeida Carneiro9Maria Fâni Dolabela10Maria Fâni Dolabela11Maria Fâni Dolabela12Sandro Percario13Sandro Percario14Postgraduate Program in Pharmaceutical Innovation, Federal University of Pará, Belém, BrazilPostgraduate Program in Biodiversity and Biotechnology, Federal University of Pará, Belém, BrazilPostgraduate Program in Pharmaceutical Innovation, Federal University of Pará, Belém, BrazilPostgraduate Program in Pharmaceutical Sciences, Federal University of Pará, Belém, BrazilPostgraduate Program in Pharmaceutical Sciences, Federal University of Pará, Belém, BrazilPostgraduate Program in Pharmaceutical Innovation, Federal University of Pará, Belém, BrazilPostgraduate Program in Biodiversity and Biotechnology, Federal University of Pará, Belém, BrazilOxidative Stress Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém, BrazilPostgraduate Program in Pharmaceutical Innovation, Federal University of Pará, Belém, BrazilNational Primate Center, Instituto Evandro Chagas, Ananindeua, BrazilPostgraduate Program in Pharmaceutical Innovation, Federal University of Pará, Belém, BrazilPostgraduate Program in Biodiversity and Biotechnology, Federal University of Pará, Belém, BrazilPostgraduate Program in Pharmaceutical Sciences, Federal University of Pará, Belém, BrazilPostgraduate Program in Biodiversity and Biotechnology, Federal University of Pará, Belém, BrazilOxidative Stress Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém, BrazilIn vitro studies with Plasmodium falciparum have demonstrated the antiparasitic activity of E. plicata, attributed to its naphthoquinones. This study reports on pro-inflammatory changes in mice infected with P. berghei and correlates these changes with parasitemia and survival. The ethanol extract of Eleutherine plicata (EEEp) was fractionated under reflux to obtain the dichloromethane fraction (FDMEp) and isolated compounds from E. plicata, relating these to survival time and parasitemia. Antimalarial activity was evaluated using the Peters suppressive test, with mice infected with Plasmodium berghei and treated with E. plicata, assessing parasitemia and survival over 30 days. The pro-inflammatory profile was determined by measuring interleukin-10, interferon-γ (IFN-γ), and nitric oxide levels. EEEp, FDMEp, and eleutherol showed activity on the 5th day of infection, with only FDMEp being active on the 8th day. Treatment with EEEp and FDMEp extended animal survival, reduced IFN-γ and NO levels, and increased IL-10 levels. Eleutherol significantly altered the response, with eleutherol glucuronide seemingly active by binding to lactate dehydrogenase, inhibiting hemozoin metabolism, leading to parasite death. Pro-inflammatory changes did not appear to correlate with survival and reduced parasitemia. In summary, FDMEp and eleutherol reduced parasitemia, extended survival, and modulated the inflammatory response. FDMEp and eleutherol are promising candidates for developing new antimalarial drugs.https://www.frontiersin.org/articles/10.3389/fphar.2024.1484934/fulleleutheroleleutherol glucuronideisoeleutherineleutherinmalaria |
| spellingShingle | Antônio Rafael Quadros Gomes Antônio Rafael Quadros Gomes Ana Laura Gadelha Castro Ana Laura Gadelha Castro Gleison Gonçalves Ferreira Heliton Patrick Cordovil Brígido Everton Luiz Pompeu Varela Everton Luiz Pompeu Varela Valdicley Vieira Vale Liliane Almeida Carneiro Maria Fâni Dolabela Maria Fâni Dolabela Maria Fâni Dolabela Sandro Percario Sandro Percario Impact on parasitemia, survival time and pro-inflammatory immune response in mice infected with Plasmodium berghei treated with Eleutherine plicata Frontiers in Pharmacology eleutherol eleutherol glucuronide isoeleutherin eleutherin malaria |
| title | Impact on parasitemia, survival time and pro-inflammatory immune response in mice infected with Plasmodium berghei treated with Eleutherine plicata |
| title_full | Impact on parasitemia, survival time and pro-inflammatory immune response in mice infected with Plasmodium berghei treated with Eleutherine plicata |
| title_fullStr | Impact on parasitemia, survival time and pro-inflammatory immune response in mice infected with Plasmodium berghei treated with Eleutherine plicata |
| title_full_unstemmed | Impact on parasitemia, survival time and pro-inflammatory immune response in mice infected with Plasmodium berghei treated with Eleutherine plicata |
| title_short | Impact on parasitemia, survival time and pro-inflammatory immune response in mice infected with Plasmodium berghei treated with Eleutherine plicata |
| title_sort | impact on parasitemia survival time and pro inflammatory immune response in mice infected with plasmodium berghei treated with eleutherine plicata |
| topic | eleutherol eleutherol glucuronide isoeleutherin eleutherin malaria |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1484934/full |
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