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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.<\/jats:p>","DOI":"10.3390\/microorganisms13020309","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T04:05:47Z","timestamp":1738296347000},"page":"309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["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"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7212-5094","authenticated-orcid":false,"given":"J\u00e9ssica Adriana","family":"Jesus","sequence":"first","affiliation":[{"name":"Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Pra\u00e7a Infante Dom Henrique, s\/n, S\u00e3o Vicente 11330-900, SP, Brazil"},{"name":"Institute for Advanced Studies of Ocean, S\u00e3o Paulo State University (UNESP), Rua Jo\u00e3o Francisco Bensdorp, 1178, S\u00e3o Vicente 11350-011, SP, Brazil"},{"name":"Laboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School, S\u00e3o Paulo University, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8560-7298","authenticated-orcid":false,"given":"Gabriela Venicia","family":"Araujo Flores","sequence":"additional","affiliation":[{"name":"Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Pra\u00e7a Infante Dom Henrique, s\/n, S\u00e3o Vicente 11330-900, SP, Brazil"},{"name":"Institute for Advanced Studies of Ocean, S\u00e3o Paulo State University (UNESP), Rua Jo\u00e3o Francisco Bensdorp, 1178, S\u00e3o Vicente 11350-011, SP, Brazil"},{"name":"Laboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School, S\u00e3o Paulo University, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalete Christine da Silva","family":"Souza","sequence":"additional","affiliation":[{"name":"Center for Natural and Human Science (CCNH), Federal University of ABC, Santo Andr\u00e9, S\u00e3o Paulo 09210-580, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2656-7454","authenticated-orcid":false,"given":"Daniela Costa","family":"Trist\u00e3o","sequence":"additional","affiliation":[{"name":"Center for Natural and Human Science (CCNH), Federal University of ABC, Santo Andr\u00e9, S\u00e3o Paulo 09210-580, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0475-8420","authenticated-orcid":false,"given":"Dolores Remedios","family":"Serrano","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Food Science, Faculty of Pharmacy, Universidad Complutense of Madrid, Plaza Ramon y Cajal s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4791-7468","authenticated-orcid":false,"given":"Aikaterina","family":"Lalatsa","sequence":"additional","affiliation":[{"name":"CRUK Formulation Unit, School of Pharmacy and Biomedical Sciences, University of Strathclyde, John Arbuthnot Building, Robertson Wing, 161 Cathedral St, Glasgow G4 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1080-2440","authenticated-orcid":false,"given":"M\u00e1rcia Dalastra","family":"Laurenti","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School, S\u00e3o Paulo University, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1193-8374","authenticated-orcid":false,"given":"Jo\u00e3o Henrique Ghilardi","family":"Lago","sequence":"additional","affiliation":[{"name":"Center for Natural and Human Science (CCNH), Federal University of ABC, Santo Andr\u00e9, S\u00e3o Paulo 09210-580, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humberto Gomes","family":"Ferraz","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9603-0770","authenticated-orcid":false,"given":"Rosana Pereira","family":"da Silva","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5986-6381","authenticated-orcid":false,"given":"Luiz Felipe Domingues","family":"Passero","sequence":"additional","affiliation":[{"name":"Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Pra\u00e7a Infante Dom Henrique, s\/n, S\u00e3o Vicente 11330-900, SP, Brazil"},{"name":"Institute for Advanced Studies of Ocean, S\u00e3o Paulo State University (UNESP), Rua Jo\u00e3o Francisco Bensdorp, 1178, S\u00e3o Vicente 11350-011, SP, Brazil"},{"name":"Laboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School, S\u00e3o Paulo University, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Corman, H.N., McNamara, C.W., and Bakowski, M.A. (2023). 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