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Analysis of the effects of the purified oleanolic and ursolic acids from Baccharis uncinella in infected BALB/c mice with Leishmania (Leishmania) amazonensis

Grant number: 12/03903-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2012
Effective date (End): December 31, 2014
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Luiz Felipe Domingues Passero
Grantee:Eduardo Seiji Yamamoto
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


The Asteraceae family is the most numerous sistematic group among the Angiosperms and for this reason they are most studied in relation to traditional uses, chemical composition and pharmacological effects. Recently, we verified that purified compost from the leaves of Baccharis uncinella (Asteraceae) had a strong leishmanicidal activity, more especifically the fraction containing oleanolic and ursolic acids induced the production of nitric oxide in infected macrophages subjected to the treatment, which presented the lower infection rates by amastigotes of L. (L.) amazonensis and L. (Viannia) braziliensis. Thus, the aim of this project is to evaluate the therapeutic effect of the purified oleanolic and ursolic acids (triterpenes) from this plant in L. (L.) amazonensis-infected BALB/c mice. The leaves of B. uncinella will be collected, dried and macerated for the production of extracts, and a series of cromatographic steps will be done for the purification of these triterpenes. After 20 days of infection, the BALB/c mice infected by L. (L.) amazonensis will be treated with different doses of these purified terpenes (to be determined in experimental protocols ours). The test groups will also be treated with antimonials or amphotercin B as standard drug. After 20 days of the last dose of both molecules, the animals will be sacrificed to determine the parasite load on skin. Cell culture will be perform with draining lymph nodes cells, which will be stimulated with total antigen of L. (L.) amazonesis promastigotes during a 48h, on which the supernatant will be collected to quantify IL-4, IL-12, IL-10 and IFN-gamma cytokines. Analysis of the humoral immune response will be carried out in the serum of BALB/c mice groups. During the experimental period, the lesion size of experimental groups will be measured weekly. This project aims to find new therapeutic targets against American tegumentar Leishmaniasis.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
YAMAMOTO, EDUARDO S.; CAMPOS, BRUNO L. S.; JESUS, JESSICA A.; LAURENTI, MARCIA D.; RIBEIRO, SUSAN P.; KALLAS, ESPER G.; RAFAEL-FERNANDES, MARIANA; SANTOS-GOMES, GABRIELA; SILVA, MARCELO S.; SESSA, DEBORAH P.; LAGO, JOAO H. G.; LEVY, DEBORA; PASSERO, LUIZ F. D. The Effect of Ursolic Acid on Leishmania (Leishmania) amazonensis Is Related to Programed Cell Death and Presents Therapeutic Potential in Experimental Cutaneous Leishmaniasis. PLoS One, v. 10, n. 12 DEC 16 2015. Web of Science Citations: 18.
YAMAMOTO, EDUARDO SEIJI; CAMPOS, BRUNO LUIZ S.; LAURENTI, MARCIA DALASTRA; LAGO, JOAO H. G.; GRECCO, SIMONE DOS SANTOS; CORBETT, CARLOS E. P.; PASSERO, LUIZ FELIPE D. Treatment with triterpenic fraction purified from Baccharis uncinella leaves inhibits Leishmania (Leishmania) amazonensis spreading and improves Th1 immune response in infected mice. Parasitology Research, v. 113, n. 1, p. 333-339, JAN 2014. Web of Science Citations: 16.

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