期刊
PARASITE IMMUNOLOGY
卷 42, 期 12, 页码 -出版社
WILEY
DOI: 10.1111/pim.12784
关键词
delivery systems; flavonoids; immune response; leishmaniasis; miltefosine; treatment
资金
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG)
- MRC [MR/R005850/1] Funding Source: UKRI
Aims Treatment for visceral leishmaniasis (VL) is hampered by the toxicity and/or high cost of drugs, as well as by emergence of parasite resistance. Therefore, there is an urgent need for new antileishmanial agents. Methods and Results In this study, the antileishmanial activity of a diprenylated flavonoid called 5,7,3,4'-tetrahydroxy-6,8-diprenylisoflavone (CMt) was tested againstLeishmania infantumandL amazonensisspecies. Results showed that CMt presented selectivity index (SI) of 70.0 and 165.0 againstL infantumandL amazonensispromastigotes, respectively, and of 181.9 and 397.8 against respective axenic amastigotes. Amphotericin B (AmpB) showed lower SI values of 9.1 and 11.1 againstL infantumandL amazonensispromastigotes, respectively, and of 12.5 and 14.3 against amastigotes, respectively. CMt was effective in the treatment of infected macrophages and caused alterations in the parasite mitochondria.L infantum-infected mice treated with miltefosine, CMt alone or incorporated in polymeric micelles (CMt/Mic) presented significant reductions in the parasite load in distinct organs, when compared to the control groups. An antileishmanial Th1-type cellular and humoral immune response were developed one and 15 days after treatment, with CMt/Mic-treated mice presenting a better protective response. Conclusion Our data suggest that CMt/Mic could be evaluated as a chemotherapeutic agent against VL.
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