title: Therapeutic effect of ursolic acid in experimental visceral leishmaniasis.
abstract: Leishmaniasis is an important neglected tropical disease, affecting more than 12 million people worldwide. The available treatments are not well tolerated and present diverse side effects in patients, justifying the search for new therapeutic compounds. In the present study, the therapeutic potential and toxicity of ursolic acid (UA), isolated from the leaves of Baccharis uncinella C. DC. (Asteraceae), were evaluated in experimental visceral leishmaniasis. To evaluate the therapeutic potential of UA, hamsters infected with L. (L.) infantum were treated daily during 15 days with 1.0 or 2.0 mg UA/kg body weight, or with 5.0 mg amphotericin B/kg body weight by intraperitoneal route. Fifteen days after the last dose, the parasitism of the spleen and liver was stimated and the main histopathological alterations were recorded. The proliferation of splenic mononuclear cells was evaluated and IFN-γ, IL-4, and IL-10 gene expressions were analyzed in spleen fragments. The toxicity of UA and amphotericin B were evaluated in healthy golden hamsters by histological analysis and biochemical parameters. Animals treated with UA had less parasites in the spleen and liver when compared with the infected control group, and they also showed preservation of white and red pulps, which correlate with a high rate of proliferation of splenic mononuclear cells, IFN-γ mRNA and iNOS production. Moreover, animals treated with UA did not present alterations in the levels of AST, ALT, creatinine and urea. Taken together, these findings indicate that UA is an interesting natural compound that should be considered for the development of prototype drugs against visceral leishmaniasis.
authors.affiliation: Laboratory 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; Center of Natural Sciences and Humanities, Federal University of ABC, Santo Andre, São Paulo, 09210-180, Brazil.
authors.forename: Jéssica A
authors.initials: JA
authors.lastname: Jesus
authors.affiliation: Laboratory 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.
authors.forename: Thais N
authors.initials: TN
authors.lastname: Fragoso
authors.affiliation: Laboratory 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.
authors.forename: Eduardo S
authors.initials: ES
authors.lastname: Yamamoto
authors.affiliation: Laboratory 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.
authors.forename: Márcia D
authors.initials: MD
authors.lastname: Laurenti
authors.affiliation: Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal; Departamento de Análises Clínicas e Toxicológicas, Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, 384, 59012-570 Natal, Brazil.
authors.forename: Marcelo S
authors.initials: MS
authors.lastname: Silva
authors.affiliation: Laboratory 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.
authors.forename: Aurea F
authors.initials: AF
authors.lastname: Ferreira
authors.affiliation: Center of Natural Sciences and Humanities, Federal University of ABC, Santo Andre, São Paulo, 09210-180, Brazil.
authors.forename: João Henrique G
authors.initials: JH
authors.lastname: Lago
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, 384, 59012-570 Natal, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Santos-Gomes
authors.affiliation: São Paulo State University (Unesp), Institute of Biosciences, São Vicente, Praça Infante Dom Henrique, s/n, 11330-900 São Vicente, SP, Brazil. Electronic address: felipepassero@clp.unesp.br.
authors.forename: Luiz Felipe D
authors.initials: LF
authors.lastname: Passero
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D031175:Baccharis / Q000737:chemistry; D055808:Drug Discovery; D005260:Female; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008099:Liver / Q000187:drug effects* / Q000469:parasitology / Q000473:pathology; D008647:Mesocricetus; D013154:Spleen / Q000187:drug effects* / Q000469:parasitology / Q000473:pathology; D014315:Triterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D000097245:Ursolic Acid
chemical_list: D000666:Amphotericin B; D000981:Antiprotozoal Agents; D007371:Interferon-gamma; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: Leishmania (Leishmania) infantum; Therapeutic potential; Toxicity; Ursolic acid