Anthelmintic Activity of the Natural Compound (+)-Limonene Epoxide against Schistosoma mansoni

Abstract

Blood fluke of the genus Schistosoma are the etiological agents of human schistosomiasis, an important neglected tropical disease that afflicts over 200 million people worldwide. The treatment for this disease relies heavily on a single drug, praziquantel. Recent reports of praziquantel resistance raise concerns about future control of the disease and show the importance of developing new antischistosomal drugs. Currently, natural products have been a good source for drug development. (+)-Limonene epoxide is a mixture of cis and trans isomers found in many plants. Here, we report the in vitro effect of this natural compound on the survival time of Schistosoma mansoni adult worms. In addition, we examined alterations on the tegumental surface of adult schistosomes by means of confocal laser scanning microscopy. The effects of (+)-limonene epoxide at 25 µg/mL on S. mansoni adult worms were similar to those of the positive control (praziquantel), with reduction in motility and death of all worms after 120 h. Confocal laser scanning microscopy revealed that (+)-limonene epoxide-mediated worm killing was associated with tegumental destruction. Our results, along with the low toxicity of the (+)-limonene epoxide, suggest that this natural compound might be promising for the development of new schistosomicidal agents.

Antischistosomal Activity of Oxindolimine-Metal Complexes

“…In this context, alterations of the tegument of S. mansoni induced by several antischistosomal compounds have also been described (25)(26)(27)(28)(29). In this study, we observed extensive tegumental damage in S. mansoni that intensified progressively when the concentrations of the oxindolimine-metal complexes tested increased.…”

Natural Products with Antischistosomal Activity

“…The mechanism by which terpenes exert their schistosomicidal effect may be that, due to inherent lipophilicity, some terpenes will easily cross plasmatic membranes and, consequently, may also interact with intracellular molecules of parasites. In fact, some of the compounds described herein are capable of causing morphological changes in the integument of worms, and a relationship has been observed between tegumental damage and the death of worms [39,56,[59][60].…”

“…The terpenes with antischistosomal activity are: rotundifolone [66], (+)-limonene epoxide [56], and carvacryl acetate, a derivative of carvacrol (monoterpenes) [39]; artemisinin and its derivatives [30,31], nerolidol [59], and budlein-A and its derivatives [38] (sesquiterpenes); phytol [60] (diterpene), betulin [37] and its triphenylphosphonium derivatives [69], balsaminol F, karavilagenin C [36] (triterpenes) (Figure 1). Importantly, among the group of terpenes, in vitro and in vivo antischistosomal properties have been described only for artemisinin and its derivatives, phytol and triphenylphosphonium derivatives, whereas it was reported in vitro schitosomicidal activity for other terpenes (Table 1).…”

In vivo and In vitro of Arctiin Schistosomicidal Activity

“…Acetate carvacrol (6.25 µg/mL) affected motility, parasite tegument and oviposition [7]. Similar results were also found for phloroglucinol derivatives (aspidina, flavaspidico acid, methylenebis-aspidinol and desaspidina) [21], dermaseptina antimicrobial peptide [27], essential oils of Piper cubeba and Tagete serecta [21,28], (+)-Epoxy-Limonene [29] and Mitracarpus frigidus methanolic extract [30].…”