Leishmanicidal and healing effects of 3β,6β,16β-trihydroxy lup-20 (29)-ene isolated from Combretum leprosum on Leishmania braziliensis infection in vitro and in vivo

Abstract

Treatment of cutaneous leishmaniasis depends on drugs that potentially cause serious side effects and resistance. Thus, topical therapies are attractive alternatives to the drugs currently used. 3β, 6β, 16β-trihydroxylup-20 (29)-ene is a lupane triterpene isolated fromCombretum leprosumMart. leaves (CLF-1), with reports ofin vitroantileishmanial effect againstL.amazonensisand to promote lesion healing in animal model. Herein, we evaluated thein vitroandin vivoantileishmanial and healing effects of CLF-1 againstL.braziliensis. CLF-1 treatment showed low toxicity in macrophages and significantly reduced parasite loadin vitro. CLF-1 induced higher IL-12 and TNF-α production and more discrete IL-4 and IL-10 production. Forin vivoevaluation, a CLF-1 cream formulation was prepared to treat hamsters infected withL.braziliensis. CLF-1 treatment was able to reduce parasite load of the infected skin and lymph node more efficiently than the conventional treatment. Histopathological analysis indicated a strong inflammatory response accompanied by an important healing response. Data from this study indicate that topical CLF-1 treatment was effective and non-toxic inL.braziliensisinfected hamsters suggesting its potential for further development as a future therapeutic intervention.