Abstract
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.
Highlights
Brazilian biodiversity has been studied extensively and increasing numbers of studies related to plant species and natural resources have contributed to new therapeutic alternatives
In mice infected by adult S. mansoni, there was a significant reduction in worm burden with oral treatment by EPIIS (Fig 3)
Because the single dose of 400 mg/kg showed no difference in terms of worm burden compared with 100 mg/kg dose, we showed the results for eggs production, liver and spleen weights, and scanning electron microscopy investigations only for the lowest dose investigated (100 mg/kg)
Summary
Brazilian biodiversity has been studied extensively and increasing numbers of studies related to plant species and natural resources have contributed to new therapeutic alternatives. An example of this development concerns the Pilocarpus microphyllus Stapf ex Wardlew species, popularly known as jaborandi, originating from North and Northeast Brazil [1,2]. Despite few studies having focused on EPIIS biological activities, its in vitro activity against S. mansoni has been previously reported [2]. These results highlighted the need to perform in vivo studies of EPIIS, primarily regarding its possible use in the treatment of schistosomiasis. It is important to evaluate possible toxicity, as acute toxicity studies in animals are used to fulfill various requirements related to the control of risks to human health and the environment [9,10]
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