Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis

Autor(es)

Jesus, Jessica Adriana ^[1] ; Fragoso da Silva, Thays Nicolli ^[1] ; Yamamoto, Eduardo Seiji ^[1] ; G. Lago, Joao Henrique ^[2] ; Dalastra Laurenti, Marcia ^[1] ; Passero, Luiz Felipe Domingues ^{[3, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Pathol, Lab Pathol Infect Dis LIM50, Ave Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil

^[2] Fed Univ ABC UFABC, Ctr Nat & Human Sci, Ave Estados 5001, BR-09210580 Santo Andre, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Inst Biosci, Praca Infante Dom Henrique S-N, BR-11330900 Sao Vicente, SP - Brazil

^[4] Sao Paulo State Univ UNESP, Inst Adv Studies Ocean, Rua Joao Francisco Bensdorp 1178, BR-11350011 Sao Vicente, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PATHOGENS; v. 9, n. 10 OCT 2020.
• Citações Web of Science: 0

Resumo

Ursolic acid (UA) is a triterpene with a broad array of pharmacological activities. In leishmaniasis, UA killed different species of parasites, and it was active in the experimental model of cutaneous and visceral leishmaniasis. Thus, the objective of this work was to study the therapeutic efficacy of the conventional drugs amphotericin B (AmB) or glucantime (Glu) combined with UA in experimental visceral and cutaneous leishmaniasis, respectively. L. (L.) infantum-infected hamsters were treated with AmB alone or combined with UA. L. (L.) amazonensis-infected BALB/c mice were treated with Glu alone or combined with UA. Animals were treated for 15 consecutive days by intraperitoneal or intralesional routes. Following one week after the last dose, the tissue parasitism and cellular immune responses were analyzed. Hamsters treated with 0.2 and 1.0 mg/kg of AmB plus 1.0 mg/kg of UA showed low hepatic and splenic parasitisms; however, AmB given as monotherapy did not reduce the number of viable parasites in the spleen of treated animals. In cutaneous leishmaniasis, Glu given as monotherapy was inactive at 2.0 mg/kg, showed mild activity at 10.0 mg/kg, and at 50.0 mg/kg was highly active at eliminating parasites in the skin. When animals were treated with Glu plus UA, higher leishmanicidal activity was observed in comparison to all groups treated with monotherapy schemes, and such activity was related to lesion improvement and upregulation of IFN-gamma production. Altogether, data suggest that the association of drugs for the treatment of leishmaniasis can increase the efficiency of the treatment and decrease the toxicity associated to the conventional drugs. (AU)

• Processo FAPESP: 18/24077-6 - Estudos pré-clínicos de tratamentos não invasivos nas leishmanioses
• Beneficiário: Luiz Felipe Domingues Passero
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/07885-1 - Biomoléculas oriundas de espécies vegetais de áreas remanescentes da Mata Atlântica e do Cerrado para tratamento de doenças tropicais negligenciadas - aspectos químicos e farmacológicos
• Beneficiário: João Henrique Ghilardi Lago
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular
• Processo FAPESP: 16/00468-0 - Uso do reposicionamento de fármacos e da bioprospecção de produtos naturais para caracterizar compostos com ação leishmanicida in vitro e in vivo
• Beneficiário: Luiz Felipe Domingues Passero
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/10324-6 - Nanopartículas lípidicas como carreadores de triterpenos para o tratamento da Leishmaniose Visceral Experimental
• Beneficiário: Jéssica Adriana de Jesus
• Modalidade de apoio: Bolsas no Brasil - Doutorado