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Exp Parasitol. 2019 Apr;199:67-73. doi: 10.1016/j.exppara.2019.02.013. Epub 2019 Feb 21.

Efficacy of lapachol on treatment of cutaneous and visceral leishmaniasis.

Author information

1
Laboratory of Bioassays in Leishmania, Institute of Biomedical Sciences, Federal University of Uberlandia, Para Avenue, 1720 - Umuarama Campus, 38400-920, Uberlandia, Minas Gerais State, Brazil.
2
Laboratory of Phytochemistry, Department of Pharmaceutical Products, Federal University of Minas Gerais, Antonio Carlos Avenue, 6627 - Pampulha Campus, 31270-901, Belo Horizonte, Minas Gerais State, Brazil.
3
Veterinary Medicine Department, Federal University of Juiz de Fora, José Lourenço Kelmerst, 36036-900, Juiz de Fora, Minas Gerais State, Brazil.
4
Laboratory of Bioassays in Leishmania, Institute of Biomedical Sciences, Federal University of Uberlandia, Para Avenue, 1720 - Umuarama Campus, 38400-920, Uberlandia, Minas Gerais State, Brazil. Electronic address: sydnei@ufu.br.

Abstract

Leishmaniasis is one of the most important neglected diseases worldwide. It is a life-threatening disease and causes significant morbidity, long-term disability, and early death. Treatment involves disease control or use of intervention measures, although the currently used drugs require long-lasting therapy, and display toxicity and reduced efficacy. The use of natural products isolated from plants, such as lapachol, an abundant naphthoquinone naturally occurring in South American Handroanthus species (Tabebuia, Bignoniaceae), is a promising option for the treatment of leishmaniasis. In this study, we investigated the leishmanicidal activity of lapachol in vitro and in vivo against Leishmania infantum and L. amazonensis, causative agents of visceral and cutaneous leishmaniasis, respectively. Low cytotoxicity in HepG2 cells (3405.8 ± 261.33 μM), good anti-Leishmania activity, and favorable selectivity indexes (SI) against promastigotes of both L. amazonensis (IC50 = 79.84 ± 9.10 μM, SI = 42.65) and L. infantum (IC50 = 135.79 ± 33.04 μM, SI = 25.08) were observed. Furthermore, anti-Leishmania activity assays performed on intracellular amastigotes showed good activity for lapachol (IC50 = 191.95 μM for L. amazonensis and 171.26 μM for L. infantum). Flow cytometric analysis demonstrated that the cytotoxic effect of lapachol in Leishmania promastigotes was caused by apoptosis-like death. Interestingly, the in vitro leishmanicidal effect of lapachol was confirmed in vivo in murine models of visceral and cutaneous leishmaniasis, as lapachol (25 mg/kg oral route for 24 h over 10 days) was able to significantly reduce the parasitic load in skin lesions, liver, and spleen, similar to amphotericin B, the reference drug. These results reinforce the therapeutic potential of lapachol, which warrants further investigations as an anti-leishmaniasis therapeutic.

KEYWORDS:

L. amazonensis; Lapachol; Leishmania infantum; Leishmaniasis; Naphthoquinones; Natural products

PMID:
30797783
DOI:
10.1016/j.exppara.2019.02.013
[Indexed for MEDLINE]

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