Meliponini Geopropolis Extracts Induce ROS Production and Death in <i>Leishmania amazonensis</i> Promastigotes and Axenic Amastigotes In Vitro
Leishmania amazonensis, a cause of cutaneous leishmaniasis in Brazil, is a neglected disease with toxic and inconsistently effective treatments. The parasite’s survival depends on managing oxidative stress, making redox-regulating enzymes potential therapeutic targets. Geopropolis, a resinous produc...
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2025-02-01
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| author | Kamila M. Sette Andreza R. Garcia Luzineide W. Tinoco Anderson S. Pinheiro Igor A. Rodrigues |
| author_facet | Kamila M. Sette Andreza R. Garcia Luzineide W. Tinoco Anderson S. Pinheiro Igor A. Rodrigues |
| author_sort | Kamila M. Sette |
| collection | DOAJ |
| description | Leishmania amazonensis, a cause of cutaneous leishmaniasis in Brazil, is a neglected disease with toxic and inconsistently effective treatments. The parasite’s survival depends on managing oxidative stress, making redox-regulating enzymes potential therapeutic targets. Geopropolis, a resinous product from native stingless bees, shows promising antiparasitic effects. This study aims to evaluate the anti-<i>L. amazonensis</i> activity of geopropolis produced by <i>Melipona bicolor</i>, <i>M. marginara</i>, <i>M. mondury</i>, and <i>M. quadrifasciata</i> (two samples), targeting enzymes responsible for the parasite’s redox balance. Ethanol extracts of geopropolis produced by each bee (BCRL, MRGT, MNDY, MNDA(1), and MNDA(2), respectively) were analyzed for total phenolics and flavonoids. Promastigotes and axenic amastigotes were treated with various extract concentrations, and parasite viability was assessed using the resazurin reduction method. Cytotoxicity was tested on peritoneal macrophages, RAW 264.7, VERO cell lines (MTT assay), and erythrocytes (hemolysis assay). Additionally, mitochondrial dehydrogenase activity, reactive oxygen species (ROS) production, the inhibition of recombinant arginase, and autophagic activity were also evaluated in treated parasites. MRGT showed the highest levels of phenolics (762 mg GAE/g) and flavonoids (345 mg QE/g). MDRY was more effective against promastigote and axenic amastigote forms (IC<sub>50</sub> = 168 and 19.7 µg/mL, respectively). MRGT showed lower cytotoxicity against RAW 264.7 and VERO (CC<sub>50</sub> = 654 µg/mL and 981 µg/mL, respectively). Erythrocytes exhibited reduced sensitivity to MNDA(2) (HC<sub>50</sub> = 710 µg/mL). The activity of dehydrogenases and <i>Li</i>ARG was reduced by treating the parasites with the extracts following the induction of ROS and autophagic activity. These results highlight geopropolis extracts as a source of substances with anti-<i>L. amazonensis</i> activity capable of inducing oxidative stress on the parasite. |
| format | Article |
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| institution | DOAJ |
| issn | 2079-7737 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-c4c437ab58e3449aa5c2ecaafd7ae35b2025-08-20T02:44:52ZengMDPI AGBiology2079-77372025-02-0114216210.3390/biology14020162Meliponini Geopropolis Extracts Induce ROS Production and Death in <i>Leishmania amazonensis</i> Promastigotes and Axenic Amastigotes In VitroKamila M. Sette0Andreza R. Garcia1Luzineide W. Tinoco2Anderson S. Pinheiro3Igor A. Rodrigues4Programa de Pós Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilPrograma de Pós Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilLaboratório Multiusuário de Análises por RMN, Instituto de Pesquisa de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilLaboratório de Bioquímica Molecular, Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilLaboratório de Investigação de Substâncias Bioativas, Departamento de Produtos Naturais, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilLeishmania amazonensis, a cause of cutaneous leishmaniasis in Brazil, is a neglected disease with toxic and inconsistently effective treatments. The parasite’s survival depends on managing oxidative stress, making redox-regulating enzymes potential therapeutic targets. Geopropolis, a resinous product from native stingless bees, shows promising antiparasitic effects. This study aims to evaluate the anti-<i>L. amazonensis</i> activity of geopropolis produced by <i>Melipona bicolor</i>, <i>M. marginara</i>, <i>M. mondury</i>, and <i>M. quadrifasciata</i> (two samples), targeting enzymes responsible for the parasite’s redox balance. Ethanol extracts of geopropolis produced by each bee (BCRL, MRGT, MNDY, MNDA(1), and MNDA(2), respectively) were analyzed for total phenolics and flavonoids. Promastigotes and axenic amastigotes were treated with various extract concentrations, and parasite viability was assessed using the resazurin reduction method. Cytotoxicity was tested on peritoneal macrophages, RAW 264.7, VERO cell lines (MTT assay), and erythrocytes (hemolysis assay). Additionally, mitochondrial dehydrogenase activity, reactive oxygen species (ROS) production, the inhibition of recombinant arginase, and autophagic activity were also evaluated in treated parasites. MRGT showed the highest levels of phenolics (762 mg GAE/g) and flavonoids (345 mg QE/g). MDRY was more effective against promastigote and axenic amastigote forms (IC<sub>50</sub> = 168 and 19.7 µg/mL, respectively). MRGT showed lower cytotoxicity against RAW 264.7 and VERO (CC<sub>50</sub> = 654 µg/mL and 981 µg/mL, respectively). Erythrocytes exhibited reduced sensitivity to MNDA(2) (HC<sub>50</sub> = 710 µg/mL). The activity of dehydrogenases and <i>Li</i>ARG was reduced by treating the parasites with the extracts following the induction of ROS and autophagic activity. These results highlight geopropolis extracts as a source of substances with anti-<i>L. amazonensis</i> activity capable of inducing oxidative stress on the parasite.https://www.mdpi.com/2079-7737/14/2/162native bee productsleishmanicidal activitymitochondrial activityhuman cutaneous leishmaniasis |
| spellingShingle | Kamila M. Sette Andreza R. Garcia Luzineide W. Tinoco Anderson S. Pinheiro Igor A. Rodrigues Meliponini Geopropolis Extracts Induce ROS Production and Death in <i>Leishmania amazonensis</i> Promastigotes and Axenic Amastigotes In Vitro Biology native bee products leishmanicidal activity mitochondrial activity human cutaneous leishmaniasis |
| title | Meliponini Geopropolis Extracts Induce ROS Production and Death in <i>Leishmania amazonensis</i> Promastigotes and Axenic Amastigotes In Vitro |
| title_full | Meliponini Geopropolis Extracts Induce ROS Production and Death in <i>Leishmania amazonensis</i> Promastigotes and Axenic Amastigotes In Vitro |
| title_fullStr | Meliponini Geopropolis Extracts Induce ROS Production and Death in <i>Leishmania amazonensis</i> Promastigotes and Axenic Amastigotes In Vitro |
| title_full_unstemmed | Meliponini Geopropolis Extracts Induce ROS Production and Death in <i>Leishmania amazonensis</i> Promastigotes and Axenic Amastigotes In Vitro |
| title_short | Meliponini Geopropolis Extracts Induce ROS Production and Death in <i>Leishmania amazonensis</i> Promastigotes and Axenic Amastigotes In Vitro |
| title_sort | meliponini geopropolis extracts induce ros production and death in i leishmania amazonensis i promastigotes and axenic amastigotes in vitro |
| topic | native bee products leishmanicidal activity mitochondrial activity human cutaneous leishmaniasis |
| url | https://www.mdpi.com/2079-7737/14/2/162 |
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