Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis
Leishmaniasis affects around 12 million people worldwide and is estimated to cause the ninth-largest disease burden. There are three main forms of the disease, visceral (VL), cutaneous (CL), and mucocutaneous (MCL), leading to more than one million new cases every year and several thousand deaths. C...
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doaj-fefd1fa637234ae0802f754e874b25742020-11-25T02:01:59ZengMDPI AGMolecules1420-30492020-03-01256139410.3390/molecules25061394molecules25061394Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral LeishmaniasisPablo Bilbao-Ramos0Dolores R. Serrano1Helga Karina Ruiz Saldaña2Juan J. Torrado3Francisco Bolás-Fernández4María Auxiliadora Dea-Ayuela5Departament of Microbiology and Parasitology, School of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, SpainDepartament of Pharmaceutics and Food Technology, School of Pharmacy, University Complutense, Avenida Complutense, 28040 Madrid, SpainDepartament of Pharmaceutics and Food Technology, School of Pharmacy, University Complutense, Avenida Complutense, 28040 Madrid, SpainDepartament of Pharmaceutics and Food Technology, School of Pharmacy, University Complutense, Avenida Complutense, 28040 Madrid, SpainDepartament of Microbiology and Parasitology, School of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, SpainDepartament of Microbiology and Parasitology, School of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, SpainLeishmaniasis affects around 12 million people worldwide and is estimated to cause the ninth-largest disease burden. There are three main forms of the disease, visceral (VL), cutaneous (CL), and mucocutaneous (MCL), leading to more than one million new cases every year and several thousand deaths. Current treatments based on chemically synthesized molecules are far from ideal. In this study, we have tested the in vitro and in vivo efficacy of ursolic acid (UA), a multifunctional triterpenoid with well-known antitumoral, antioxidant, and antimicrobial effects on different <i>Leishmania</i> strains. The in vitro antileishmanial activity against the intracellular forms was six and three-fold higher compared to extracellular forms of <i>L. amazonensis</i> and <i>L. infantum,</i> respectively. UA also showed to be a potent antileishmanial drug against both VL and CL manifestations of the disease in experimental models. UA parenterally administered at 5 mg/kg for seven days significantly reduced the parasite burden in liver and spleen not only in murine acute infection but also in a chronic-infection model against <i>L. infantum</i>. In addition, UA ointment (0.2%) topically administered for four weeks diminished (50%) lesion size progression in a chronic infection model of CL caused by <i>L. amazonensis,</i> which was much greater than the effect of UA formulated as an O/W emulsion. UA played a key role in the immunological response modulating the Th1 response. The exposure of <i>Leishmania-</i>infected macrophages to UA led to a significant different production in the cytokine levels depending on the <i>Leishmania</i> strain causing the infection. In conclusion, UA can be a promising therapy against both CL and VL.https://www.mdpi.com/1420-3049/25/6/1394ursolic acidvisceral leishmaniasisacute-infectionchronic-infectioncutaneous leishmaniasiscytokines |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pablo Bilbao-Ramos Dolores R. Serrano Helga Karina Ruiz Saldaña Juan J. Torrado Francisco Bolás-Fernández María Auxiliadora Dea-Ayuela |
spellingShingle |
Pablo Bilbao-Ramos Dolores R. Serrano Helga Karina Ruiz Saldaña Juan J. Torrado Francisco Bolás-Fernández María Auxiliadora Dea-Ayuela Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis Molecules ursolic acid visceral leishmaniasis acute-infection chronic-infection cutaneous leishmaniasis cytokines |
author_facet |
Pablo Bilbao-Ramos Dolores R. Serrano Helga Karina Ruiz Saldaña Juan J. Torrado Francisco Bolás-Fernández María Auxiliadora Dea-Ayuela |
author_sort |
Pablo Bilbao-Ramos |
title |
Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis |
title_short |
Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis |
title_full |
Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis |
title_fullStr |
Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis |
title_full_unstemmed |
Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis |
title_sort |
evaluating the potential of ursolic acid as bioproduct for cutaneous and visceral leishmaniasis |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2020-03-01 |
description |
Leishmaniasis affects around 12 million people worldwide and is estimated to cause the ninth-largest disease burden. There are three main forms of the disease, visceral (VL), cutaneous (CL), and mucocutaneous (MCL), leading to more than one million new cases every year and several thousand deaths. Current treatments based on chemically synthesized molecules are far from ideal. In this study, we have tested the in vitro and in vivo efficacy of ursolic acid (UA), a multifunctional triterpenoid with well-known antitumoral, antioxidant, and antimicrobial effects on different <i>Leishmania</i> strains. The in vitro antileishmanial activity against the intracellular forms was six and three-fold higher compared to extracellular forms of <i>L. amazonensis</i> and <i>L. infantum,</i> respectively. UA also showed to be a potent antileishmanial drug against both VL and CL manifestations of the disease in experimental models. UA parenterally administered at 5 mg/kg for seven days significantly reduced the parasite burden in liver and spleen not only in murine acute infection but also in a chronic-infection model against <i>L. infantum</i>. In addition, UA ointment (0.2%) topically administered for four weeks diminished (50%) lesion size progression in a chronic infection model of CL caused by <i>L. amazonensis,</i> which was much greater than the effect of UA formulated as an O/W emulsion. UA played a key role in the immunological response modulating the Th1 response. The exposure of <i>Leishmania-</i>infected macrophages to UA led to a significant different production in the cytokine levels depending on the <i>Leishmania</i> strain causing the infection. In conclusion, UA can be a promising therapy against both CL and VL. |
topic |
ursolic acid visceral leishmaniasis acute-infection chronic-infection cutaneous leishmaniasis cytokines |
url |
https://www.mdpi.com/1420-3049/25/6/1394 |
work_keys_str_mv |
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