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Schistosomiasis is a disease caused by parasites of the genus  Schistosoma , currently affecting more than 200 million people. Among the various species of this parasite that infect humans,  S .  mansoni  is the most common. Pharmacological treatment is limited to the use of a single drug, praziquantel (PZQ), despite reports of parasite resistance and low efficacy. It is therefore necessary to investigate new potential schistosomicidal compounds. In this study, we tested the efficacy of epiisopilosine (EPIIS) in a murine model of schistosomiasis. A single dose of EPIIS (100 or 400 mg/kg) administered orally to mice infected with adult  S .  mansoni  resulted in reduced worm burden and egg production. The treatment with the lower dose of EPIIS (100 mg/kg) significantly reduced total worm burden by 60.61% ( P  < 0.001), as well as decreasing hepatosplenomegaly and egg excretion. Scanning electron microscopy revealed morphological changes in the worm tegument after treatment. Despite good activity of EPIIS in adult  S .  mansoni , oral treatment with single dose of EPIIS 100 mg/kg had only moderate effects in mice infected with juvenile  S .  mansoni . In addition, we performed cytotoxicity and toxicological studies with EPIIS and found no  in vitro  cytotoxicity (in HaCaT, and NIH-3T3 cells) at a concentration of 512 μg/mL. We also performed  in silico  analysis of toxicological properties and showed that EPIIS had low predicted toxicity. To confirm this, we investigated systemic acute toxicity  in vivo  by orally administering a 2000 mg/kg dose to Swiss mice. Treated mice showed no significant changes in hematological, biochemical, or histological parameters compared to non-treated animals. Epiisopilosine showed potential as a schistosomicidal drug: it did not cause acute toxicity and it displayed an acceptable safety profile in the animal model.

Epiisopilosine alkaloid has activity against Schistosoma mansoni in mice without acute toxicity