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Article

Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis

1
Departament of Microbiology and Parasitology, School of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain
2
Laboratorio de Parasitología y Entomología INLASA, Pasaje Rafael Zubieta #1889, (Lado Estado Mayor del ejército) Zona Miraflores, La Paz, Bolivia
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Departament of Pharmaceutics and Food Technology, School of Pharmacy, University Complutense, Avenida Complutense, 28040 Madrid, Spain
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Institute of Industrial Pharmacy (IUFI), Plaza Ramon y Cajal, SN, 28040 Madrid, Spain
5
Departament of Pharmacy, School of Health Science, Universidad CEU Cardenal Herrera, C/Ramón y Cajal s/n, 46115 Alfara del Patriarca (Valencia), Spain
*
Author to whom correspondence should be addressed.
Academic Editors: Manuela Pintado, Ezequiel Coscueta and María Emilia Brassesco
Molecules 2020, 25(6), 1394; https://doi.org/10.3390/molecules25061394
Received: 12 February 2020 / Revised: 10 March 2020 / Accepted: 15 March 2020 / Published: 19 March 2020
(This article belongs to the Special Issue Bioproducts for Health)
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 Leishmania strains. The in vitro antileishmanial activity against the intracellular forms was six and three-fold higher compared to extracellular forms of L. amazonensis and L. infantum, 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 L. infantum. 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 L. amazonensis, 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 Leishmania-infected macrophages to UA led to a significant different production in the cytokine levels depending on the Leishmania strain causing the infection. In conclusion, UA can be a promising therapy against both CL and VL. View Full-Text
Keywords: ursolic acid; visceral leishmaniasis; acute-infection; chronic-infection; cutaneous leishmaniasis; cytokines ursolic acid; visceral leishmaniasis; acute-infection; chronic-infection; cutaneous leishmaniasis; cytokines
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MDPI and ACS Style

Bilbao-Ramos, P.; Serrano, D.R.; Ruiz Saldaña, H.K.; Torrado, J.J.; Bolás-Fernández, F.; Dea-Ayuela, M.A. Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis. Molecules 2020, 25, 1394. https://doi.org/10.3390/molecules25061394

AMA Style

Bilbao-Ramos P, Serrano DR, Ruiz Saldaña HK, Torrado JJ, Bolás-Fernández F, Dea-Ayuela MA. Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis. Molecules. 2020; 25(6):1394. https://doi.org/10.3390/molecules25061394

Chicago/Turabian Style

Bilbao-Ramos, Pablo, Dolores R. Serrano, Helga K. Ruiz Saldaña, Juan J. Torrado, Francisco Bolás-Fernández, and María A. Dea-Ayuela. 2020. "Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis" Molecules 25, no. 6: 1394. https://doi.org/10.3390/molecules25061394

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