Evidence map›Paper›PMID 26674781›Full record

ArticlePloS one2015

The Effect of Ursolic Acid on Leishmania (Leishmania) amazonensis Is Related to Programed Cell Death and Presents Therapeutic Potential in Experimental Cutaneous Leishmaniasis.

Eduardo S Yamamoto, Bruno L S Campos, Jéssica A Jesus, Márcia D Laurenti, Susan P Ribeiro, Esper G Kallás, Mariana Rafael-Fernandes, Gabriela Santos-Gomes, Marcelo S Silva, Deborah P Sessa and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
6.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 83 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
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  8. Frontiers in molecular biosciences · 2023
    Article
  9. Human Lung Cancer (A549) Cell Line Cytotoxicity and Anti-Pharmaceuticals (Basel, Switzerland) · 2022
    Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Leishmanicidal Activity and Ultrastructural Changes of Maslinic Acid Isolated fromEvidence-based complementary and alternative medicine : eCAM · 2021
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 3 countries.

Eduardo S YamamotoLaboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School of São Paulo University, Av. Dr. Arnaldo, 455. Cerqueira César, São Paulo, 01246-903, SP, Brazil.
Bruno L S CamposLaboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School of São Paulo University, Av. Dr. Arnaldo, 455. Cerqueira César, São Paulo, 01246-903, SP, Brazil.
Jéssica A JesusLaboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School of São Paulo University, Av. Dr. Arnaldo, 455. Cerqueira César, São Paulo, 01246-903, SP, Brazil.
Márcia D LaurentiLaboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School of São Paulo University, Av. Dr. Arnaldo, 455. Cerqueira César, São Paulo, 01246-903, SP, Brazil.
Susan P RibeiroLaboratory of Clinical Immunology and Allergy (LIM60), University of São Paulo, School of Medicine. Av. Dr. Arnaldo, 455. Cerqueira César, São Paulo, Brazil.
Esper G KallásLaboratory of Clinical Immunology and Allergy (LIM60), University of São Paulo, School of Medicine. Av. Dr. Arnaldo, 455. Cerqueira César, São Paulo, Brazil.
Mariana Rafael-FernandesGlobal Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal.
Gabriela Santos-GomesGlobal Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal.
Marcelo S SilvaGlobal Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal.
Deborah P SessaInstitute of Environmental, Chemical and Pharmaceutical Sciences - Federal University of São Paulo, Rua São Nicolau, 210, 09920-000, Diadema, SP, Brazil.
João H G LagoInstitute of Environmental, Chemical and Pharmaceutical Sciences - Federal University of São Paulo, Rua São Nicolau, 210, 09920-000, Diadema, SP, Brazil.
Débora LevyLaboratory of Genetics and Molecular Hematology (LIM31), University of São Paulo, School of Medicine. Av. Dr. Enéas de Carvalho Aguiar, 155. Cerqueira César, São Paulo, Brazil.
Luiz F D PasseroLaboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School of São Paulo University, Av. Dr. Arnaldo, 455. Cerqueira César, São Paulo, 01246-903, SP, Brazil.
Universidade de São Paulo · BRUniversidade Nova de Lisboa · PTUniversidade Federal de São Paulo · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Among 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 nitric oxide (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.

Indexed as

AnimalsApoptosisCytokinesDisease Models, AnimalFemaleLeishmaniaLeishmaniasis, CutaneousMacrophages, PeritonealMaleMiceNitric OxideOleanolic AcidPlant ExtractsTriterpenesTrypanocidal AgentsUrsolic AcidCytokinesNitric OxideOleanolic AcidPlant ExtractsTriterpenesTrypanocidal AgentsUrsolic Acid

Identifiers

PMID26674781
PMCPMC4699202
OpenAlexW2221023436

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.