Parasitology Research

, Volume 118, Issue 1, pp 369–376 | Cite as

6,7-Dehydroroyleanone diterpene derived from Tetradenia riparia essential oil modulates IL-4/IL-12 release by macrophages that are infected with Leishmania amazonensis

  • Mariana de Souza Terron-MonichEmail author
  • Izabel Galhardo Demarchi
  • Pollyanna Rina Ferreira da Silva
  • Áquila Carolina Fernandes Herculano Ramos-Milaré
  • Zilda Cristiani Gazim
  • Thaís Gomes Verzignassi Silveira
  • Maria Valdrinez Campana Lonardoni
Immunology and Host-Parasite Interactions - Short Communication


The treatment of cutaneous leishmaniasis in associated with several adverse effects and therapeutic failure, resulting in patients’ abandonment of treatment. Research on new drugs with leishmanicidal potential from medicinal plants is essential. The anti-Leishmania activity of Tetradenia riparia essential oil (TrEO) and its derivatives, such as the diterpene 6,7-dehydroroyleanone (TrROY), and the immunomodulatory effects of TrEO have been reported. However, few studies have investigated the effects of TrROY. The present study evaluated the modulation of cytokine production by murine macrophages that were infected with Leishmania amazonensis (6 parasites/macrophage) and treated with TrROY (0.1, 1, and 100 μg/ml). Cytokine levels were measured by flow cytometry. The results were analyzed using Student’s t test at a 95% confidence interval. Microscopic counting was performed to evaluate the inhibitory effects of TrROY on intracellular infection. TrROY modulated the production of cytokines that are essential for the immune defense response to Leishmania, with a decrease in interleukin-4 (IL-4) levels and an increase in IL-12 levels. A TrROY concentration of 0.1 μg/ml was chosen for the subsequent experiments. This dose was chosen because it modulated IL-4/IL-12 release by murine macrophages that were infected with Leishmania and because it presented no cytotoxic effects. TrROY (0.1 μg/ml) induced a 31% reduction of the rate of infection in murine macrophages compared with untreated cells. TrROY may be a promising leishmanicidal agent. Further in vitro and in vivo studies should be conducted to evaluate the anti-Leishmania and immunomodulatory activity of TrROY.


6,7-Dehydroroyleanone diterpene Tetradenia riparia essential oil Leishmania amazonensis 


Funding information

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil, supported this work.

Compliance with ethical standards

This study was approved by the Committee of Ethics in Animal Use in Experiments (CEAE) of the State University of Maringá (Paraná, Brazil; opinion nos. 133/2012 and 079/2012) to obtain cells from BALB/c mice.

Conflict of interest

The authors declare that there is no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Mariana de Souza Terron-Monich
    • 1
    • 2
    Email author
  • Izabel Galhardo Demarchi
    • 1
    • 2
  • Pollyanna Rina Ferreira da Silva
    • 3
  • Áquila Carolina Fernandes Herculano Ramos-Milaré
    • 1
    • 2
  • Zilda Cristiani Gazim
    • 4
  • Thaís Gomes Verzignassi Silveira
    • 2
  • Maria Valdrinez Campana Lonardoni
    • 2
  1. 1.Postgraduation Program in Health SciencesUniversidade Estadual de MaringáMaringáBrazil
  2. 2.Department of Clinical Analysis and BiomedicineUniversidade Estadual de MaringáMaringáBrazil
  3. 3.Graduation in PharmacyUniversidade Estadual de MaringáMaringáBrazil
  4. 4.Chemical of Natural Products LaboratoryUniversidade ParanaenseUmuaramaBrazil

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