Avaliação do potencial da licochalcona a na terapia da esquistossomose in vitro e em modelo murino

Abstract

Schistosomiasis, one significant neglected tropical disease, is an infection caused by trematode worms of the genus Schistosoma spp. it is endemic in 78 countries, being a major public health challenge. Currently, the absence of an effective vaccine supports the chemotherapy as the mainstay of schistosomiasis control programs. However, the chemotherapy has limitations, such as, the emergence of praziquantel-resistant strains. In recent years, attempts to discover new antischistosomal drugs had remarkable contribution of natural products. In this context, the flavonoid Licochalcona A - chemotaxonomic marker of the specie Glycyrrhiza inflata - has several biological activities such as anti-inflammatory, antioxidant and anti-protozoan against species of Leishmania spp. and Plasmodium spp. Moreover, Licochalcona A showed promising schistosomicidal activity in a preliminary study. Thus, the aim of this study was to evaluate the progression of schistosomiasis in Swiss mice treated with LicoA and it activity against adult worms in vitro. After 24 hour incubation, concentrations from 50μM LicoA caused tegument darkening, moderate loss of motility and areas of swelling body. Moreover, the exposure to the compound produced accumulation of resorufin and hence the discontinuity in the labelling of the main branches and tubules in the excretory system of schistosomes. The latter may be the source of other effects, contributing to the understanding of the potential influence of the drug on receptors and / or enzymes in schistosomes. In addition, the alleged partial inhibition of SmATPDases can also contribute to the failure of parasitism. In vivo tests, the 50 mg/kg schedule of two doses administered intraperitoneally were the most promising reached a median 25% reduction of worm burden and increased hepatic displacement of the worms. Moreover, the drug did not induce changes in the qualitative or oogram liver and spleen weight relative inertia about showing the kinetics of oviposition. Further studies should be conducted to collect evidence on the effect of schistosomicidal Licochalcona A, especially those that consider a larger number of animals and analyzed parameters, such as the profile of in vivo cytokines and chemokines, and other in vitro methods and the improvement of those who were employed here in order to provide more details on the influence of LicoA in some systems intrinsic to the parasite.