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Some medicinal plants, used traditionally for the treatment of worm infections, contain cysteine proteinases known to damage worms irreversibly<jats:italic>in vitro<\/jats:italic>. Here we (i) confirm that papaya latex has marked efficacy<jats:italic>in vivo<\/jats:italic>against the rodent gastrointestinal nematode,<jats:italic>Heligmosomoides polygyrus<\/jats:italic>, (ii) demonstrate the dose-dependent nature of the activity (&gt;90% reduction in egg output and 80% reduction in worm burden at the highest active enzyme concentration of 133\u00a0nmol), (iii) establish unequivocally that it is the cysteine proteinases that are the active principles<jats:italic>in vivo<\/jats:italic>(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<jats:italic>in vitro<\/jats:italic>, 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.<\/jats:p>","DOI":"10.1017\/s0031182007002867","type":"journal-article","created":{"date-parts":[[2007,5,3]],"date-time":"2007-05-03T17:02:01Z","timestamp":1178211721000},"page":"1409-1419","source":"Crossref","is-referenced-by-count":43,"title":["The anthelmintic efficacy of plant-derived cysteine proteinases against the rodent gastrointestinal nematode,<i>Heligmosomoides polygyrus<\/i>,<i>in 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