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Microorganisms
Volume 13
Issue 2
10.3390/microorganisms13020309
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Dicentrine Purified from the Leaves of Ocotea puberula Controls the Intracellular Spread of L. (L.) amazonensis and L. (V.) braziliensis Amastigotes and Has Therapeutic Activity as a Topical Treatment in Experimental Cutaneous Leishmaniasis

by
Jéssica Adriana Jesus
1,2,3,
Gabriela Venicia Araujo Flores
1,2,3,
Dalete Christine da Silva Souza
4,
Daniela Costa Tristão
4,
Dolores Remedios Serrano
5,
Aikaterina Lalatsa
6,
Márcia Dalastra Laurenti
3,
João Henrique Ghilardi Lago
4,
Humberto Gomes Ferraz
7,
Rosana Pereira da Silva
7 and
Luiz Felipe Domingues Passero
1,2,3,*
1
Institute of Biosciences, São Paulo State University (UNESP), Praça Infante Dom Henrique, s/n, São Vicente 11330-900, SP, Brazil
2
Institute for Advanced Studies of Ocean, São Paulo State University (UNESP), Rua João Francisco Bensdorp, 1178, São Vicente 11350-011, SP, Brazil
3
Laboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School, São Paulo University, São Paulo 01246-903, SP, Brazil
4
Center for Natural and Human Science (CCNH), Federal University of ABC, Santo André, São Paulo 09210-580, SP, Brazil
5
Department of Pharmaceutics and Food Science, Faculty of Pharmacy, Universidad Complutense of Madrid, Plaza Ramon y Cajal s/n, 28040 Madrid, Spain
6
CRUK Formulation Unit, School of Pharmacy and Biomedical Sciences, University of Strathclyde, John Arbuthnot Building, Robertson Wing, 161 Cathedral St, Glasgow G4 0RE, UK
7
Pharmaceutical Development and Innovation Laboratory (Deinfar), Department of Pharmacy, School of Pharmaceutical Sciences, University of Sao Paulo, Professor Lineu Prestes Avenue, Sao Paulo 05508-580, SP, Brazil
*
Author to whom correspondence should be addressed.
Microorganisms 2025, 13(2), 309; https://doi.org/10.3390/microorganisms13020309
Submission received: 13 December 2024 / Revised: 14 January 2025 / Accepted: 21 January 2025 / Published: 30 January 2025
(This article belongs to the Special Issue Research on Leishmania and Leishmaniasis)
Versions Notes

Abstract

Leishmaniasis, a complex disease caused by protozoal parasites of the genus Leishmania, presents various clinical forms, particularly a cutaneous clinical form. Treatment is typically performed with pentavalent antimonial and amphotericin B, both of which have severe side effects that hinder patient compliance. This emphasizes the need for the development of new, effective, and safe treatments. In this study, the leishmanicidal activity of the methanolic extract, an alkaloid-enriched fraction and dicentrine, the main alkaloid of the leaves of Ocotea puberula (Lauraceae), a native Brazilian plant traditionally used by the indigenous population to treat skin affections, was investigated in vitro. Additionally, an in vivo study evaluated the efficacy of a topical cream containing 0.5% dicentrine. The in vitro studies demonstrated high activity and selectivity of methanolic extract, alkaloid-enriched fraction, and dicentrine against the promastigote and amastigote forms of Leishmania (Leishmnia) amazonensis and Leishmania (Viannia) braziliensis. The leishmanicidal effect of dicentrine was related to the modulation of macrophage microbicidal activity. A cream containing 0.5% dicentrine showed high stability and, in permeation studies, dicentrine was retained in a skin-mimicking artificial membrane. This cream effectively inhibited the progression of the skin lesion in BALB/c mice infected with L. (L.) amazonensis, together with a reduced parasite number. Thus, dicentrine offers a promising alternative to the treatment of skin leishmaniasis.
Keywords: Ocotea puberula; Leishmania (Leishmania) amazonensis; Leishmania (Viannia) braziliensis; treatment Ocotea puberula; Leishmania (Leishmania) amazonensis; Leishmania (Viannia) braziliensis; treatment

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MDPI and ACS Style

Jesus, J.A.; Araujo Flores, G.V.; Souza, D.C.d.S.; Tristão, D.C.; Serrano, D.R.; Lalatsa, A.; Laurenti, M.D.; Lago, J.H.G.; Ferraz, H.G.; da Silva, R.P.; et al. Dicentrine Purified from the Leaves of Ocotea puberula Controls the Intracellular Spread of L. (L.) amazonensis and L. (V.) braziliensis Amastigotes and Has Therapeutic Activity as a Topical Treatment in Experimental Cutaneous Leishmaniasis. Microorganisms 2025, 13, 309. https://doi.org/10.3390/microorganisms13020309

AMA Style

Jesus JA, Araujo Flores GV, Souza DCdS, Tristão DC, Serrano DR, Lalatsa A, Laurenti MD, Lago JHG, Ferraz HG, da Silva RP, et al. Dicentrine Purified from the Leaves of Ocotea puberula Controls the Intracellular Spread of L. (L.) amazonensis and L. (V.) braziliensis Amastigotes and Has Therapeutic Activity as a Topical Treatment in Experimental Cutaneous Leishmaniasis. Microorganisms. 2025; 13(2):309. https://doi.org/10.3390/microorganisms13020309

Chicago/Turabian Style

Jesus, Jéssica Adriana, Gabriela Venicia Araujo Flores, Dalete Christine da Silva Souza, Daniela Costa Tristão, Dolores Remedios Serrano, Aikaterina Lalatsa, Márcia Dalastra Laurenti, João Henrique Ghilardi Lago, Humberto Gomes Ferraz, Rosana Pereira da Silva, and et al. 2025. "Dicentrine Purified from the Leaves of Ocotea puberula Controls the Intracellular Spread of L. (L.) amazonensis and L. (V.) braziliensis Amastigotes and Has Therapeutic Activity as a Topical Treatment in Experimental Cutaneous Leishmaniasis" Microorganisms 13, no. 2: 309. https://doi.org/10.3390/microorganisms13020309

APA Style

Jesus, J. A., Araujo Flores, G. V., Souza, D. C. d. S., Tristão, D. C., Serrano, D. R., Lalatsa, A., Laurenti, M. D., Lago, J. H. G., Ferraz, H. G., da Silva, R. P., & Passero, L. F. D. (2025). Dicentrine Purified from the Leaves of Ocotea puberula Controls the Intracellular Spread of L. (L.) amazonensis and L. (V.) braziliensis Amastigotes and Has Therapeutic Activity as a Topical Treatment in Experimental Cutaneous Leishmaniasis. Microorganisms, 13(2), 309. https://doi.org/10.3390/microorganisms13020309

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