In vitro and in vivo evaluation of cnicin from blessed thistle (Centaurea benedicta) and its inclusion complexes with cyclodextrins against Schistosoma mansoni

Schistosomiasis, caused by a blood fluke of the genus Schistosoma, afflicts over 230 million people worldwide. Treatment of the disease relies on just one drug, praziquantel. Cnicin (Cn) is the sesquiterpene lactone found in blessed thistle (Centaurea benedicta) that showed antiparasitic activities but has not been evaluated against Schistosoma. However, cnicin has poor water solubility, which may limit its antiparasitic activities. To overcome these restrictions, inclusion complexes with cyclodextrins may be used. In this work, we evaluated the in vitro and in vivo antischistosomal activities of cnicin and its complexes with beta-cyclodextrin (beta CD) and 2-hydroxypropyl-beta-cyclodextrin (HP beta CD) against Schistosoma mansoni. Cnicin were isolated from C. benedicta by chromatographic fractionation. Complexes formed by cnicin and beta CD (Cn/beta CD), as well as by cnicin and HP beta CD (Cn/HP beta CD), were prepared by coprecipitation and characterized. In vitro schistosomicidal assays were used to evaluate the effects of cnicin and its complexes on adult schistosomes, while the in vivo antischistosomal assays were evaluated by oral and intraperitoneal routes. Results showed that cnicin caused mortality and tegumental alterations in adult schistosomes in vitro, also showing in vivo efficacy after intraperitoneal administration. The oral treatment with cnicin or Cn/beta CD showed no significant worm reductions in a mouse model of schistosomiasis. In contrast, Cn/HP beta CD complex, when orally or intraperitoneally administered to S. mansoni-infected mice, decreased the total worm load, and markedly reduced the number of eggs, showing high in vivo antischistosomal effectiveness. Permeability studies, using Nile red, indicated that HP beta CD complex may reach the tegument of adult schistosomes in vivo. These results demonstrated the antischistosomal potential of cnicin in preparations with HP beta CD.