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

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Jesus, Jessica Adriana ; Araujo Flores, Gabriela Venicia ; Souza, Dalete Christine da Silva ; Tristao, Daniela Costa ; Serrano, Dolores Remedios ; Lalatsa, Aikaterina ; Laurenti, Marcia Dalastra ; Lago, Joao Henrique Ghilardi ; Ferraz, Humberto Gomes ; da Silva, Rosana Pereira ; Passero, Luiz Felipe Domingues

• Document type: Journal article
• Source: MICROORGANISMS; v. 13, n. 2, p. 17-pg., 2025-02-01.

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. (AU)

• FAPESP's process: 22/15834-3 - REPOSITIONING OF DRUGS FOR THE TREATMENT OF EXPERIMENTAL NON-ULCERATED CUTANEOUS LEISHMANIASIS CAUSED BY Leishmania (L.) infantum chagasi
• Grantee: Gabriela Venicia Araujo Flores
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/50315-0 - Leishmaniasis in Latin America: an advanced perspective on immunopathogenetic factors of cutaneous and visceral infection, immunomodulators of the sandflies vector saliva and immunogenic exo-antigens of Leishmania (L.) infantum chagasi as vaccine candidates
• Grantee: Marcia Dalastra Laurenti
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 23/12447-1 - Searching for specialized metabolites from Brazilian floristic biodiversity as drug candidates for neglected tropical diseases
• Grantee: João Henrique Ghilardi Lago
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants
• FAPESP's process: 23/01641-1 - Looking for new therapeutic alternatives for Leishmaniasis
• Grantee: Luiz Felipe Domingues Passero
• Support Opportunities: Regular Research Grants