In vitro and in vivo anthelmintic efficacy of plant cysteine proteinases against the rodent gastrointestinal nematode, Trichuris muris

Stepek, Gillian; Lowe, Ann; Buttle, David J.; Duce, I.R.; Behnke, Jerzy M.

doi:10.1017/s003118200500973x

Cited by 84 publications

(100 citation statements)

References 37 publications

(51 reference statements)

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“…Although the plant cysteine proteinases, with the exception of actinidain, show anthelmintic activity against P. muricola in vitro, and earlier studies have shown significant in vivo efficacy of papaya latex against the adult worms of H. polygyrus (Stepek et al manuscript in preparation) and T. muris (Stepek et al 2006), we initially failed to detect efficacy of papaya latex against P. muricola in vivo. However, when the mice were pre-treated with the antacid cimetidine, papaya latex had a significant anthelmintic effect.…”

Section: Discussionmentioning

confidence: 78%

“…This was followed by complete digestion of the cuticle by 120 min. As with H. polygyrus (Stepek et al 2005) and T. muris (Stepek et al 2006), the adult worms of P. muricola were not affected by the cysteine proteinase from kiwi fruit, actinidain (Fig. 3D).…”

Section: R E S U L T Smentioning

confidence: 75%

“…In earlier studies, we reported significant reductions in parasite egg output and worm burden of H. polygyrus (Stepek et al manuscript in preparation) and T. muris (Stepek et al 2006), when infected mice were treated with papaya latex. For consistency, we also tested papaya latex here against P. muricola in vivo to determine whether this representative source of plant-derived cysteine proteinases would show comparable activity against a stomach nematode.…”

Section: In Vivo Assessment Of Anthelmintic Efficacy Of Plant Cysteinmentioning

confidence: 76%

“…Four control worms (1 worm/ well) were incubated with either 25 mM (active enzyme) papaya latex+150 mM E-64, 75 mM (active enzyme) stem bromelain+300 mM E-64, Hanks' saline with 16 mM L-cysteine or Hanks' saline alone. The worms were incubated at 37 xC for 2 h, and their motility was recorded every 15 min using a motility scale from 0-5, where 0 is completely immobile and 5 is highly active (Stepek et al 2005(Stepek et al , 2006.…”

Section: Enzymesmentioning

confidence: 99%

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Anthelmintic action of plant cysteine proteinases against the rodent stomach nematode,Protospirura muricola,in vitroandin vivo

et al. 2006

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A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. Cysteine proteinases from the fruit and latex of plants, including papaya, pineapple and fig, were previously shown to have a rapid detrimental effect, in vitro, against the rodent gastrointestinal nematodes, Heligmosomoides polygyrus (which is found in the anterior small intestine) and Trichuris muris (which resides in the caecum). Proteinases in the crude latex of papaya also showed anthelmintic efficacy against both nematodes in vivo. In this paper, we describe the in vitro and in vivo effects of these plant extracts against the rodent nematode, Protospirura muricola, which is found in the stomach. As in earlier work, all the plant cysteine proteinases examined, with the exception of actinidain from the juice of kiwi fruit, caused rapid loss of motility and digestion of the cuticle, leading to death of the nematode in vitro. In vivo, in contrast to the efficacy against H. polygyrus and T. muris, papaya latex only showed efficacy against P. muricola adult female worms when the stomach acidity had been neutralized prior to administration of papaya latex. Therefore, collectively, our studies have demonstrated that, with the appropriate formulation, plant cysteine proteinases have efficacy against nematodes residing throughout the rodent gastrointestinal tract.

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Section: Discussionmentioning

confidence: 78%

Section: R E S U L T Smentioning

confidence: 75%

Section: In Vivo Assessment Of Anthelmintic Efficacy Of Plant Cysteinmentioning

confidence: 76%

Section: Enzymesmentioning

confidence: 99%

See 2 more Smart Citations

Anthelmintic action of plant cysteine proteinases against the rodent stomach nematode,Protospirura muricola,in vitroandin vivo

et al. 2006

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“…However, to our knowledge, the current study is the first (i) to establish, unequivocally, that it is upon the cysteine proteinases present in the latex that the anthelmintic efficacy of papaya latex depends, and (ii) to provide evidence that the mechanisms of action in vivo and in vitro are essentially indistinguishable. In vitro studies (Stepek et al 2005(Stepek et al , 2006(Stepek et al , 2007 have demonstrated that cysteine proteinases attack the protective cuticle of the nematode, rapidly leading to complete dissolution of the parasite, a mechanism of action that differs from all the current anthelmintic drugs (Sangster and Gill, 1999 ;Martin and Robertson, 2000). This effect was similar to that described previously for 3 other gastrointestinal nematodes, H. polygyrus (Stepek et al 2005), T. muris (Stepek et al 2006) and Ascaris suum (Robbins, 1930 ;Berger and Asenjo, 1939), indicating that plant cysteine proteinases have a broad spectrum of activity against GI nematodes in vitro.…”

Section: Discussionmentioning

confidence: 99%

The anthelmintic efficacy of plant-derived cysteine proteinases against the rodent gastrointestinal nematode,Heligmosomoides polygyrus,in vivo

Stepek

Lowe²,

Buttle

et al. 2007

Parasitology

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A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.ukThe anthelmintic efficacy of plant-derived cysteine proteinases against the rodent gastrointestinal nematode, Heligmosomoides polygyrus, in vivo Gastrointestinal (GI) nematodes are important disease-causing organisms, controlled primarily through treatment with synthetic drugs, but the efficacy of these drugs has declined due to widespread resistance, and hence new drugs, with different modes of action, are required. Some medicinal plants, used traditionally for the treatment of worm infections, contain cysteine proteinases known to damage worms irreversibly in vitro. Here we (i) confirm that papaya latex has marked efficacy in vivo against the rodent gastrointestinal nematode, Heligmosomoides polygyrus, (ii) demonstrate the dosedependent nature of the activity (>90 % reduction in egg output and 80 % reduction in worm burden at the highest active enzyme concentration of 133 nmol), (iii) establish unequivocally that it is the cysteine proteinases that are the active principles in vivo (complete inhibition of enzyme activity when pre-incubated with the cysteine proteinase-specific inhibitor, E-64) and (iv) show that activity is confined to worms that are in the intestinal lumen. The mechanism of action was distinct from all current synthetic anthelmintics, and was the same as that in vitro, with the enzymes attacking and digesting the protective cuticle. Treatment had no detectable side-effects on immune cell numbers in the mucosa (there was no difference in the numbers of mast cells and goblet cells between the treated groups) and mucosal architecture (length of intestinal villi). Only the infected and untreated mice had much shorter villi than the other 3 groups, which was a consequence of infection and not treatment. Plant-derived cysteine proteinases are therefore prime candidates for development as novel drugs for the treatment of GI nematode infections.

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Bromelain

Amini¹,

Masoumi-Moghaddam²,

Morris³

2016

Utility of Bromelain and N-Acetylcysteine in Treatment of Peritoneal Dissemination of Gastrointestinal Mucin-Producing Malignan

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In vitro and in vivo anthelmintic efficacy of plant cysteine proteinases against the rodent gastrointestinal nematode, Trichuris muris

Abstract: (2006) In vitro and in vivo anthelmintic efficacy of plant cysteine proteinases against the rodent gastrointestinal nematode, Trichuris muris. Parasitology, 132 (5).

Cited by 84 publications

References 37 publications

Anthelmintic action of plant cysteine proteinases against the rodent stomach nematode,Protospirura muricola,in vitroandin vivo

Anthelmintic action of plant cysteine proteinases against the rodent stomach nematode,Protospirura muricola,in vitroandin vivo

The anthelmintic efficacy of plant-derived cysteine proteinases against the rodent gastrointestinal nematode,Heligmosomoides polygyrus,in vivo

Bromelain

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