Abstract
Among neglected tropical diseases, leishmaniasis is one of the most important ones, affecting more than 12 million people worldwide. The available treatments are not well tolerated, and present diverse side effects, justifying the search for new therapeutic compounds. In the present study, the activity of ursolic acid (UA) and oleanolic acid (OA) were assayed in experimental cutaneous leishmaniasis (in vitro and in vivo). Promastigote forms of L. amazonensis were incubated with OA and UA for 24h, and effective concentration 50% (EC50) was estimated. Ultraestructural alterations in Leishmania amazonensis promastigotes after UA treatment were evaluated by transmission electron microscopy, and the possible mode of action was assayed through Annexin V and propidium iodide staining, caspase 3/7 activity, DNA fragmentation and transmembrane mitochondrial potential. The UA potential was evaluated in intracellular amastigotes, and its therapeutic potential was evaluated in L. amazonensis infected BALB/c mice. UA eliminated L. amazonensis promastigotes with an EC50 of 6.4 μg/mL, comparable with miltefosine, while OA presented only a marginal effect on promastigote forms at 100 μg/mL. The possible mechanism by which promastigotes were eliminated by UA was programmed cell death, independent of caspase 3/7, but it was highly dependent on mitochondria activity. UA was not toxic for peritoneal macrophages from BALB/c mice, and it was able to eliminate intracellular amastigotes, associated with nitric oxide (NO) production. OA did not eliminate amastigotes nor trigger NO. L. amazonensis infected BALB/c mice submitted to UA treatment presented lesser lesion size and parasitism compared to control. This study showed, for the first time, that UA eliminate promastigote forms through a mechanism associated with programed cell death, and importantly, was effective in vivo. Therefore, UA can be considered an interesting candidate for future tests as a prototype drug for the treatment of cutaneous leishmaniasis.
Highlights
Leishmaniasis is an infectious disease caused by a protozoan belonging to the Leishmania genus (Kinetoplastida: Trypanosomatidae) and transmitted to humans through the bite of insect vectors, such as Lutzomyia sp. and Phlebotomus sp. [1]
Results showed that ursolic acid (UA) eliminated L. (L.) amazonensis promastigote in a dose-dependent manner, showing an effective concentration 50% (EC50) of 6.2 ± 1.8 μg/
UA isolated from Baccharis dracunculifolia was effective against L. donovani promastigotes with an EC50 of 3.7 μg/ mL
Summary
Leishmaniasis is an infectious disease caused by a protozoan belonging to the Leishmania genus (Kinetoplastida: Trypanosomatidae) and transmitted to humans through the bite of insect vectors, such as Lutzomyia sp. and Phlebotomus sp. [1]. The cutaneous form of leishmaniasis can be caused by a diverse of Leishmania species, a spectrum of clinical signs can be recorded, ranging from a single localized skin lesion, that can heal spontaneously, to multiple ulcerated or non-ulcerated lesions affecting skin and/or mucosa, and these types of lesions frequently require a more complex treatment [3]. The most accepted hypothesis is that SbV acts as a pro-drug and upon administration in humans, a considerable fraction is reduced to its more toxic counterpart SbIII, causing parasite death. How this reduction occurs is unknown, it can be caused through enzymatic reaction or even mediated by plasma or cellular thiols present on the host’s cell phagosomes [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
