Efficacy of lapachol on treatment of cutaneous and visceral leishmaniasis

• Published in: Experimental parasitology Vol. 199; pp. 67 - 73
• Main Authors: Araújo, Iasmin Aparecida Cunha, de Paula, Renata Cristina, Alves, Ceres Luciana, Faria, Karen Ferraz, Oliveira, Marco Miguel de, Mendes, Gabriela Gonçalves, Dias, Eliane Martins Ferreira Abdias, Ribeiro, Raul Rio, Oliveira, Alaíde Braga de, Silva, Sydnei Magno da
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2019
• Subjects: L. amazonensis; Lapachol; Leishmania infantum; Leishmaniasis; Naphthoquinones; Natural products; Leishmania infantum; Lapachol; Leishmaniasis; Natural products; Naphthoquinones; L. amazonensis
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2019.02.013

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.
Lapachol induces apoptosis in Leishmania sp. and shows potential therapeutic potential for leishmaniasis. [Display omitted]
•Lapachol demonstrates leishmanicidal activity in vitro.•Lapachol induced apoptosis-like death in Leishmania promastigotes.•In vivo, lapachol reduced the parasitic load in skin lesions, liver, and spleen.