The in vivo effect of natural compounds on Leishmania (L.) amazonensis.

TRONCOSO ME; GAMARRA LUQUES C; GERMANO MJ; CIFUENTES D; LOZANO E; SOSA LOCHEDINO A; CARGNELUTTI DE

Buenos Aires

Congreso; Drug Discovery for Neglected Diseases International Congress.; 2018

Instituto de Química y Metabolismo del Fármaco (IQUIMEFA) (UBA-CONICET)

Introduction: The leishmaniases are a spectrum of diseases caused by infection with protozoan pathogens of the Leishmania genus, with an estimated 2 million new cases per annum (1). Leishmania parasites are transmitted to a mammalian host via the bite of an infected sand fly. The clinical forms of the disease (cutaneous, mucocutaneous and visceral leishmaniasis) depend on the species of Leishmania involved. In Argentina, affects the northern region of the country with an incidence that has increased over the last two decades. Current treatments for leishmaniasis are unsatisfactory due to high associated toxicity, cost, complex administration and the emergence of resistant strains. Efforts have greatly increased over the last decade to identify novel compounds with anti-leishmanial properties. Thus, one strategy in the search for new compounds is the screening of molecules purified from plant sources. Terpenes appear as good candidates, because they are abundant in the plant kingdom and some of them have shown a significant activity against trypanosomatids. The diterpene 5-epi-icetexone (ICTX), isolated from Salvia gilliessi, is effective against T. cruzi and Leishmania spp (2). Moreover, there are more than five hundred species of plants in Mendoza province, central west Argentina for which ?folkloric medicine? has described several uses to preserve and aid health (3). Tessaria absinthioides (Ts) and Prosopis strombulifera (Ps) have been used as an astringent, anti-inflammatory and anti-diarrheal agent (4. 5). Recent studies have confirmed its biological activities against different microorganisms (6-8). The aqueous extracts (Aq) of both plants, TaAq and PsAq, have been shown to be not toxic in experimental animals (9, 10). Objective: Evaluate the effect of ICTX, PsAq and TaAq in an in vivo model of cutaneous leishmaniasis. Materials and methods: Male BALB/c mice were infected in the right footpad with 1x105 promastigotes of L (L.) amazonensis and localy treated (4 days), with 1 mg/animal/day of ICTX. PsAq and TaAq were administrated oraly by diluting them in the drinking water. PsAq 150 mg/animal/day and TaAq 300 mg/animal/day for 10 weeks. We analyze footpad swelling, parasite load and IgG levels to determine the effectiveness of the treatments. Results and discussion: We observe that the treatment with the compounds decreases footpad swelling compared to the controls. This is related to the significant decrease in parasite load and IgG levels observed with every treatment. Conclusion: Although many more analyzes should be made, these natural compounds could be effective to treat cutaneous leishmaniasis.