Anthelmintic Activity In Vivo of Epiisopiloturine against Juvenile and Adult Worms of Schistosoma mansoni

Abstract

Schistosomiasis is a serious disease currently estimated to affect more that 207 million people worldwide. Due to the intensive use of praziquantel, there is increasing concern about the development of drug-resistant strains. Therefore, it is necessary to search for and investigate new potential schistosomicidal compounds. This work reports the in vivo effect of the alkaloid epiisopiloturine (EPI) against adults and juvenile worms of Schistosoma mansoni. EPI was first purified its thermal behavior and theoretical solubility parameters charaterised. In the experiment, mice were treated with EPI over the 21 days post-infection with the doses of 40 and 200 mg/kg, and 45 days post-infection with single doses of 40, 100 and 300 mg/kg. The treatment with EPI at 40 mg/kg was more effective in adult worms when compared with doses of 100 and 300 mg/kg. The treatment with 40 mg/kg in adult worms reduced parasite burden significantly, lead to reduction in hepatosplenomegaly, reduced the egg burden in faeces, and decreased granuloma diameter. Scanning electron microscopy revealed morphological changes to the parasite tegument after treatment, including the loss of important features. Additionally, the in vivo treatment against juvenile with 40 mg/kg showed a reduction of the total worm burden of 50.2%. Histopathological studies were performed on liver, spleen, lung, kidney and brain and EPI was shown to have a DL50 of 8000 mg/kg. Therefore EPI shows potential to be used in schistosomiasis treatment. This is the first time that schistosomicidal in vivo activity of EPI has been reported.

In Vitro and In Vivo Studies of Spironolactone as an Antischistosomal Drug Capable of Clinical Repurposing

“…This finding could be attributed to a high reduction in the worm burden as a result of treatment with spironolactone and/or inhibition of oviposition by adult helminths. A significant reduction in eggs collected from the intestine (oogram) or feces has been described with other antischistosomal compounds (21)(22)(23). In addition, the pathology normally associated with the deposition of schistosome eggs in the spleen and liver was clearly ameliorated, mainly when spironolactone was administered for 5 days.…”

“…For scanning electron microscopy, control and treated adult parasites were fixed for at least 3 h in 2.5% glutaraldehyde (Sigma) at room temperature. Experimental protocols for scanning electron microscopy were published previously (22,23). Samples were metalized with gold using a Desk II sputter coater (Denton Vacuum LLC, Moorestown, NJ) and then observed using a JEOL SM-6460LV high-resolution scanning electron microscopy (JEOL, Ltd., Tokyo, Japan).…”

In vitro anthelmintic activity and chemical composition of methanol extracts and fractions of Croton paraguayensis and Vernonia brasiliana against Eisenia fetida

“…Regarding V. brasiliana, the analysis showed the presence of alkaloids, tannins and steroids and/or triterpenes. The presence of alkaloids in both plants is important, given that many articles can be found in the literature that refer to the anthelmintic activity of these compounds [7,12,13].…”

In vivo and In vitro of Arctiin Schistosomicidal Activity

“…Fabri et al [30] demonstrated that treatment with methanolic extract of M. frigidus avoided increase of liver and spleen weight during S. mansoni infection. Studies with epiisopiloturina alkali at dosage of 40 mg/kg achieved similar results and the effects with higher doses were not satisfactory [27,32]. Treatment with arctiin at concentration of 50 mg/kg had not impact on liver weight, since no statistically significant difference was found when compared with control groups.…”