Page 346 - Resúmen - XXV Congreso Latinoamericano de Parasitología - FLAP

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Leishmanicidal activity of maslinic acid, ursolic acid, betulin and lupeol

loaded onto lipid nanoencarriers

de Jesus, Jéssica Adriana ; da Silva, Thays Nicolli F. ; Tomokane, Thaíse Yumie ;
1
1
1
Laurenti, Márcia Dalastra ; Passero, Luiz Felipe D.
1
2
1 Medical School of São Paulo University (FMUSP); São Paulo State University (Unesp)
2

Prospecting natural plant-isolated compounds may be a promising alternative for treating leishmaniasis that
affects millions of people around the world. Thus, the present study compared the in vitro effects of the
triterpenes maslinic acid (MA), ursolic acid (UA), betulin (Be) and lupeol (Lu), as well as their possible
cellular targets in L. (L.) infantum as well as the therapeutic potential of the most active triterpenes in
nanostructured lipid carriers (NLC). These compounds were commercially obtained. MA, UA and Lu were
active against promastigote and amastigote forms of L. infantum. The triterpene Be showed no significant
leishmanicidal effect against amastigote forms. Parasites were incubated with the effective concentrations
50% (EC50) of the triterpenes for 24h, and ultrastructural analyzes were performed. The main alterations
were related to the formation of vesicular compartments with or without myelin figures or rest of membranes,
as well as intracellular organelles disruption, especially parasite mitochondria, that was swelled and
fragmented; additionally its membrane potential was altered after 15 minutes of incubation with all studied
triterpenes. Parasite chromatin was also fragmented, suggesting that triterpenes induce programmed cell
death. Results show that the UA and Lu triterpenes encapsulated in NLC were more active in eliminating
amastigotes during treatment in vivo when compared to free triterpene or empty nanoparticles, presenting
significant reduction in splenic and hepatic parasitic load of hamsters infected with L. infantum and treated
with UA-NLC and Lu-NLC. The results indicate that UA and Lu triterpenes are interesting targets for the
development of new classes of drugs against leishmaniasis, since the in vitro effects were comparable to
miltefosine, presented low cytotoxicity and high selectivity. Thus these molecules can be considered
promising candidates for the treatment of visceral leishmaniasis.

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