The anthelmintic efficacy of natural plant cysteine proteinases againstHymenolepis microstoma in vivo

Abstract

Little is known about the efficacy of cysteine proteinases (CP) as anthelmintics for cestode infections in vivo. Hymenolepis microstoma is a natural parasite of house mice, and provides a convenient model system for the assessment of novel drugs for anthelmintic activity against cestodes. The experiments described in this paper indicate that treatment of H. microstoma infections in mice with the supernatant of papaya latex (PLS), containing active cysteine proteinases, is only minimally efficacious. The statistically significant effects seen on worm burden and biomass showed little evidence of dose dependency, were temporary and the role of cysteine proteinases as the active principles in PLS was not confirmed by specific inhibition with E-64. Worm fecundity was not affected by treatment at the doses used. We conclude also that this in vivo host-parasite system is not sensitive enough to be used reliably for the detection of cestocidal activity of compounds being screened as potential, novel anthelmintics.

The anthelmintic efficacy of natural plant cysteine proteinases against the rat tapeworm Hymenolepis diminutain vivo

“…The results reported in this paper provide the first convincing evidence that entirely lumen-dwelling tapeworms, such as H. diminuta , are adversely affected by CPs in vivo, albeit moderately and not nearly as severely as nematodes in mice, sheep and pigs (Stepek et al , 2007b; Buttle et al , 2011; Levecke et al , 2014). This contrasts with previous reports based on experiments with the rodent tapeworms H. nana and H. microstoma in mice, in which fruit-derived CPs were found to be without any, or with just minor, effects on tapeworm infections (He et al , 1992; de Amorin et al , 1999; Mansur et al , 2014b). Disappointingly, our results (fig.…”

“…The enzymes used in this study were cysteine proteinases (CPs) found in the supernatant of papaya latex, prepared as described previously (Buttle et al , 2011; Luoga et al , 2012; Mansur et al , 2014a, b). Papaya latex contains four cysteine proteinases: chymopapain, glycyl endopeptidase, caricain and papain (in order of relative abundance (Buttle et al , 1990)).…”

“…In comparison, data concerning the effects of CPs against cestode infections are rather inconclusive. While CPs were able to kill cestodes in vitro (He et al , 1992; Stepek et al , 2007c; Mansur et al , 2014a), they were not able to reduce parasite burdens in mice infected with Hymenolepis nana (He et al , 1992; de Amorin et al , 1999) and were also only minimally efficacious against Hymenolepis microstoma in vivo (Mansur et al , 2014b). These results, however, may be partially attributed to the use of inappropriate model systems: unlike most cestodes, H. nana does not have an absolute dependence on intermediate hosts and can re-infect its host through autoinfection, and the scolex of H. microstoma is largely protected due to its location in the bile duct, at some distance from the lumen of the intestine where most of any orally delivered, non-absorbed drug would reside during its passage through the gut (Smyth, 1976).…”

The anthelmintic efficacy of natural plant cysteine proteinases against the equine tapeworm, Anoplocephala perfoliatain vitro

“…Papaya latex has been demonstrated to be efficacious against lumen-dwelling stages of murine (Stepek et al , 2007c), porcine (Satrija et al , 1994; Levecke et al , 2014), ovine (Buttle et al , 2011) and canine (Stepek et al , 2007d) nematodes, and even nematodes of poultry (Mursof & He, 1991). It has also been shown to affect the juvenile stages of plant parasitic nematodes (Stepek et al , 2007a) and some efficacy has been observed against rodent-parasitic tapeworms at both in vitro and in vivo levels (Mansur et al , 2014, 2015). Efficacy against the free-living Caenorhabditis elegans has also been reported (Phiri et al , 2014).…”

“…Conventional chemotherapy is largely based on synthetic products, but an alternative source of anthelmithic agents may reside in the promising developments of plant-based anthelmintics, such as the cysteine proteinases (CPs) found naturally in plant latices and the juices of fruits, as for example in pineapples, figs and papaya (Behnke et al , 2008). Plant-derived CPs have been shown to have powerful anthelmintic effects on various parasitic nematodes ranging from murine (Stepek et al , 2007b, c) to ovine (Buttle et al , 2011) and porcine (Levecke et al , 2014), and recent work shows that they are also effective against tapeworms (Stepek et al , 2007d; Mansur et al , 2014, 2015). In this paper we present data assessing in vitro the efficacy of papaya latex and pineapple extracts against the equine cestode A. perfoliata , a species that is not easy to treat with conventional anthelmintics (Matthews et al , 2004).…”