In vivo schistosomicidal activity of 7-epiclusianone and its quantification in the plasma of healthy and Schistosoma mansoni infected mice using UPLC-MS/MS.

BACKGROUND: The tetraprenylated benzophenone 7-epiclusianone (7-epi) is a substance isolated from the fruits of Garcinia brasiliensis and in vitro studies have demonstrated that 7-epi is effective against Schistosoma mansoni adult worms. HYPOTHESIS/PURPOSE: Here we report the in vivo evaluation of 7-epi and its pharmacokinetic in healthy and Schistosoma mansoni infected mice. STUDY DESIGN AND METHODS: In this work, we assayed the schistosomicidal activity of 7-epi at the dose of 100 mg/kg and 300 mg/kg body weight/day in S. mansoni experimentally infected mice. Besides, two groups of animals were treated and a detailed analysis of plasma samples was performed by liquid chromatography coupled to mass spectrometry (LC-MS/MS). RESULTS: The worm burden showed a reduction in the infected mice after treatment with 300 mg/kg for five days (p < .05). And we found an increase of AUC0-∞ (20846 vs. 32438 ng.h/ml) and a decrease of total apparent clearance (0.006 vs. 0.004 l/h/kg) of 7- epi in the infected group compared to the healthy group. Consequently, the half-life increased (1.73 vs. 6.11 h) and Cmax was reduced (5427.5 vs. 3321.0 ng/ml) in the infected group compared to the healthy group. In addition, histopathological investigations were performed analysing liver samples from healthy and infected mice. CONCLUSION: The results showed significant schistosomicidal in vivo activity at 300 mg/kg. In addition, livers from S. mansoni infected mice showed a greater number of egg granulomas and the changes in the pharmacokinetic parameters in this group could be associated with the pathology of the murine experimental schistosomiasis.

In vitro evaluation of the schistosomicidal effect of the extracts, fractions and major 3-hydroxy-2,6-dialkyl-substituted piperidine alkaloids from the flowers of Senna spectabilis (Fabaceae).

In this work, we present the in vitro schistosomicidal activity evaluation of the most active dichloromethane fraction (FDm) (ED50=83.5µg/mL) and of a mixture of the major alkaloids ((-)-cassine/(-)-spectaline, C/E) (ED50=37.4µg/mL) from the flowers of Senna spectabilis against adult worms and cercariae. We also demonstrate other toxic effects including paralysis of the adult worms, inhibition of the secretory activity, tegument lesions and cercaricidal activity. In the association test of Praziquantel (PZQ)-C/E, we observed up to 80% mortality of Schistosoma mansoni in comparison to PZQ monotherapy. Due to the diversity of the toxic effects, the schistosomicidal activity of C/E is likely a result of a multitarget mechanism involving the tegument, secretory system and neuromotor action.