The effect of ursolic acid on leishmania (Leishmania) amazonensis is related to programed cell death and presents therapeutic potential in experimental cutaneous leishmaniasis
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| Publication Date: | 2015 |
| Other Authors: | , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Source: | Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
| Download full: | https://doi.org/10.1371/journal.pone.0144946 |
Summary: | PMID: 26674781 WOS:000366722700076 |
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The effect of ursolic acid on leishmania (Leishmania) amazonensis is related to programed cell death and presents therapeutic potential in experimental cutaneous leishmaniasisAgricultural and Biological Sciences(all)Biochemistry, Genetics and Molecular Biology(all)Medicine(all)SDG 3 - Good Health and Well-beingPMID: 26674781 WOS:000366722700076Among neglected tropical diseases, leishmaniasis is one of the most important ones, affecting more than 12 million people worldwide. The available treatments are not well tolerated, and present diverse side effects, justifying the search for new therapeutic compounds. In the present study, the activity of ursolic acid (UA) and oleanolic acid (OA) were assayed in experimental cutaneous leishmaniasis (in vitro and in vivo). Promastigote forms of L. amazonensis were incubated with OA and UA for 24h, and effective concentration 50% (EC50) was estimated. Ultraestructural alterations in Leishmania amazonensis promastigotes after UA treatment were evaluated by transmission electron microscopy, and the possible mode of action was assayed through Annexin V and propidium iodide staining, caspase 3/7 activity, DNA fragmentation and transmembrane mitochondrial potential. The UA potential was evaluated in intracellular amastigotes, and its therapeutic potential was evaluated in L. amazonensis infected BALB/c mice. UA eliminated L. amazonensis promastigotes with an EC50 of 6.4 μg/mL, comparable with miltefosine, while OA presented only a marginal effect on promastigote forms at 100 μg/mL. The possible mechanism by which promastigotes were eliminated by UA was programmed cell death, independent of caspase 3/7, but it was highly dependent on mitochondria activity. UA was not toxic for peritoneal macrophages from BALB/c mice, and it was able to eliminate intracellular amastigotes, associated with nitricoxide (NO) production. OA did not eliminate amastigotes nor trigger NO. L. amazonensis infected BALB/c mice submitted to UA treatment presented lesser lesion size and parasitism compared to control. This study showed, for the first time, that UA eliminate promastigote forms through a mechanism associated with programed cell death, and importantly, was effective in vivo. Therefore, UA can be considered an interesting candidate for future tests as a prototype drug for the treatment of cutaneous leishmaniasis.Global Health and Tropical Medicine (GHTM)Instituto de Higiene e Medicina Tropical (IHMT)Vector borne diseases and pathogens (VBD)RUNYamamoto, Eduardo S.Campos, Bruno L SJesus, Jéssica A.Laurenti, Márcia D.Ribeiro, Susan P.Kallás, Esper G.Rafael-Fernandes, MarianaSantos-Gomes, GabrielaSilva, Marcelo S.Sessa, Deborah P.Lago, João H GLevy, DéboraPassero, Luiz F D2018-05-11T22:03:10Z2015-12-012015-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://doi.org/10.1371/journal.pone.0144946eng1932-6203PURE: 1733426http://www.scopus.com/inward/record.url?scp=84956613295&partnerID=8YFLogxKhttps://doi.org/10.1371/journal.pone.0144946info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-22T17:32:36Zoai:run.unl.pt:10362/36594Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:03:34.544681Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse |
| dc.title.none.fl_str_mv |
The effect of ursolic acid on leishmania (Leishmania) amazonensis is related to programed cell death and presents therapeutic potential in experimental cutaneous leishmaniasis |
| title |
The effect of ursolic acid on leishmania (Leishmania) amazonensis is related to programed cell death and presents therapeutic potential in experimental cutaneous leishmaniasis |
| spellingShingle |
The effect of ursolic acid on leishmania (Leishmania) amazonensis is related to programed cell death and presents therapeutic potential in experimental cutaneous leishmaniasis Yamamoto, Eduardo S. Agricultural and Biological Sciences(all) Biochemistry, Genetics and Molecular Biology(all) Medicine(all) SDG 3 - Good Health and Well-being |
| title_short |
The effect of ursolic acid on leishmania (Leishmania) amazonensis is related to programed cell death and presents therapeutic potential in experimental cutaneous leishmaniasis |
| title_full |
The effect of ursolic acid on leishmania (Leishmania) amazonensis is related to programed cell death and presents therapeutic potential in experimental cutaneous leishmaniasis |
| title_fullStr |
The effect of ursolic acid on leishmania (Leishmania) amazonensis is related to programed cell death and presents therapeutic potential in experimental cutaneous leishmaniasis |
| title_full_unstemmed |
The effect of ursolic acid on leishmania (Leishmania) amazonensis is related to programed cell death and presents therapeutic potential in experimental cutaneous leishmaniasis |
| title_sort |
The effect of ursolic acid on leishmania (Leishmania) amazonensis is related to programed cell death and presents therapeutic potential in experimental cutaneous leishmaniasis |
| author |
Yamamoto, Eduardo S. |
| author_facet |
Yamamoto, Eduardo S. Campos, Bruno L S Jesus, Jéssica A. Laurenti, Márcia D. Ribeiro, Susan P. Kallás, Esper G. Rafael-Fernandes, Mariana Santos-Gomes, Gabriela Silva, Marcelo S. Sessa, Deborah P. Lago, João H G Levy, Débora Passero, Luiz F D |
| author_role |
author |
| author2 |
Campos, Bruno L S Jesus, Jéssica A. Laurenti, Márcia D. Ribeiro, Susan P. Kallás, Esper G. Rafael-Fernandes, Mariana Santos-Gomes, Gabriela Silva, Marcelo S. Sessa, Deborah P. Lago, João H G Levy, Débora Passero, Luiz F D |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Global Health and Tropical Medicine (GHTM) Instituto de Higiene e Medicina Tropical (IHMT) Vector borne diseases and pathogens (VBD) RUN |
| dc.contributor.author.fl_str_mv |
Yamamoto, Eduardo S. Campos, Bruno L S Jesus, Jéssica A. Laurenti, Márcia D. Ribeiro, Susan P. Kallás, Esper G. Rafael-Fernandes, Mariana Santos-Gomes, Gabriela Silva, Marcelo S. Sessa, Deborah P. Lago, João H G Levy, Débora Passero, Luiz F D |
| dc.subject.por.fl_str_mv |
Agricultural and Biological Sciences(all) Biochemistry, Genetics and Molecular Biology(all) Medicine(all) SDG 3 - Good Health and Well-being |
| topic |
Agricultural and Biological Sciences(all) Biochemistry, Genetics and Molecular Biology(all) Medicine(all) SDG 3 - Good Health and Well-being |
| description |
PMID: 26674781 WOS:000366722700076 |
| publishDate |
2015 |
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2015-12-01 2015-12-01T00:00:00Z 2018-05-11T22:03:10Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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https://doi.org/10.1371/journal.pone.0144946 |
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https://doi.org/10.1371/journal.pone.0144946 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
1932-6203 PURE: 1733426 http://www.scopus.com/inward/record.url?scp=84956613295&partnerID=8YFLogxK https://doi.org/10.1371/journal.pone.0144946 |
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