Hostname: page-component-745bb68f8f-f46jp Total loading time: 0 Render date: 2025-02-10T13:20:28.897Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  01 February 2006

G. STEPEK ,
A. E. LOWE ,
D. J. BUTTLE ,
I. R. DUCE  and
J. M. BEHNKE
G. STEPEK
Affiliation:
School of Biology, University Park, University of Nottingham NG7 2RD, UK
A. E. LOWE
Affiliation:
School of Biology, University Park, University of Nottingham NG7 2RD, UK
D. J. BUTTLE
Affiliation:
Division of Genomic Medicine, University of Sheffield S10 2RX, UK
I. R. DUCE
Affiliation:
School of Biology, University Park, University of Nottingham NG7 2RD, UK
J. M. BEHNKE
Affiliation:
School of Biology, University Park, University of Nottingham NG7 2RD, UK
Get access Rights & Permissions [Opens in a new window]

Abstract

Extracts of plants, such as papaya, pineapple and fig, are known to be effective at killing intestinal nematodes that inhabit anterior sites in the small intestine, such as Heligmosomoides polygyrus. In this paper, we demonstrate that similar in vitro efficacy also occurs against a rodent nematode of the large intestine, Trichuris muris, and confirm that the cysteine proteinases present in the plant extracts are the active principles. The mechanism of action of these enzymes involved an attack on the structural proteins of the nematode cuticle, which was similar to that observed with H. polygyrus. However, not all plant cysteine proteinases were equally efficacious because actinidain, from the juice of kiwi fruit, had no detrimental effect on either the motility of the worms or the nematode cuticle. Papaya latex was also shown to significantly reduce both worm burden and egg output of mice infected with adult T. muris, demonstrating that enzyme activity survived passage to the caecum and was not completely inactivated by the acidity of the host's stomach or destroyed by the gastric or pancreatic proteinases. Thus, the cysteine proteinases from plants may be a much-needed alternative to currently available anthelmintic drugs due to their efficacy and novel mode of action against different gastrointestinal nematode species.

Keywords

plant cysteine proteinasespapayafigpineapplekiwi fruitgastrointestinal nematodesanthelminticTrichuris muris
Type
Research Article
Information
Parasitology , Volume 132 , Issue 5 , May 2006 , pp. 681 - 689
Copyright
2006 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Albonico, M., Bickle, Q., Ramsan, M., Montresor, A., Savioli, L. and Taylor, M. ( 2003). Efficacy of mebendazole and levamisole alone or in combination against intestinal nematode infections after repeated targeted mebendazole treatment in Zanzibar. Bulletin of the World Health Organization 81, 343–352.Google Scholar
Baker, E. N. ( 1980). Structure of actinidin, after refinement at 1.7 Å resolution. Journal of Molecular Biology 141, 441–484.Google Scholar
Behnke, J. M. and Wakelin, D. ( 1973). The survival of Trichuris muris in wild populations of its natural hosts. Parasitology 67, 157–164.CrossRefGoogle Scholar
Berger, J. and Asenjo, C. F. ( 1939). Anthelmintic activity of fresh pineapple juice. Science 90, 299–300.CrossRefGoogle Scholar
Berger, J. and Asenjo, C. F. ( 1940). Anthelmintic activity of crystalline papain. Science 91, 387–388.CrossRefGoogle Scholar
Brocklehurst, K., Baines, B. S. and Malthouse, J. P. G. ( 1981). Differences in the interactions of the catalytic groups of the active centres of actinidin and papain. The Biochemical Journal 197, 739–746.CrossRefGoogle Scholar
Chan, M.-S. ( 1997). The global burden of intestinal nematode infections – fifty years on. Parasitology Today 13, 438–443.CrossRefGoogle Scholar
De Clercq, D., Sacko, M., Behnke, J., Gilbert, F., Dorny, P. and Vercruysse, J. ( 1997). Failure of mebendazole in treatment of human hookworm infections in the southern region of Mali. American Journal of Tropical Medicine and Hygiene 57, 25–30.CrossRefGoogle Scholar
Fahmy, M. A. M. ( 1954). An investigation on the life cycle of Trichuris muris. Parasitology 44, 50–57.CrossRefGoogle Scholar
Hansson, A., Veliz, G., Naquira, C., Amren, M., Arroyo, M. and Arevalo, G. ( 1986). Preclinical and clinical studies with latex from Ficus glabrata HBK, a traditional intestinal anthelmintic in the Amazonian area. Journal of Ethnopharmacology 17, 105–138.CrossRefGoogle Scholar
Horton, J. ( 2003). Human gastrointestinal helminth infections: are they now neglected diseases? Trends in Parasitology 19, 527–531.Google Scholar
Jackson, F. and Coop, R. L. ( 2000). The development of anthelmintic resistance in sheep nematodes. Parasitology 120 (Suppl.), S95–S107.CrossRefGoogle Scholar
Kaminsky, R. ( 2003). Drug resistance in nematodes: a paper tiger or a real problem? Current Opinion in Infectious Diseases 16, 559–564.Google Scholar
Kaplan, R. M. ( 2004). Drug resistance in nematodes of veterinary importance: a status report. Trends in Parasitology 20, 477–481.CrossRefGoogle Scholar
Kowlessur, D., O'Driscoll, M., Topham, C. M., Templeton, W., Thomas, E. W. and Brocklehurst, K. ( 1989). The interplay of electrostatic fields and binding interactions determining catalytic-site reactivity in actinidin. The Biochemical Journal 259, 443–452.CrossRefGoogle Scholar
Kramer, D. E. and Whitaker, J. R. ( 1964). Ficus enzymes II: Properties of the proteolytic enzymes from the latex of Ficus carica variety Kadota. Journal of Biological Chemistry 239, 2178–2183.Google Scholar
Lee, T. D. G. and Wakelin, D. ( 1982). Cortisone-induced immunotolerance to nematode infection in CBA/Ca mice I: Investigation of the defect in the protective response. Immunology 47, 227–232.Google Scholar
Lee, T. D. G. and Wright, K. A. ( 1978). The morphology of the attachment and probable feeding site of the nematode Trichuris muris (Schrank, 1788) Hall, 1916. Canadian Journal of Zoology 56, 1889–1905.CrossRefGoogle Scholar
Martin, R. J., Robertson, A. P. and Bjorn, H. ( 1997). Target sites of anthelmintics. Parasitology 114 (Suppl.), S111–S124.Google Scholar
Michel, J. F. ( 1985). Strategies for the use of anthelmintics in livestock and their implications for the development of drug resistance. Parasitology 90, 621–628.CrossRefGoogle Scholar
Mwamachi, D. M., Audho, J. O., Thorpe, W. and Baker, R. L. ( 1995). Evidence for multiple anthelmintic resistance in sheep and goats reared under the same management in coastal Kenya. Veterinary Parasitology 60, 303–313.CrossRefGoogle Scholar
Nokes, C., Grantham-McGregor, S. M., Sawyer, A. W., Cooper, E. S., Robinson, B. A. and Bundy, D. A. P. ( 1992). Moderate to heavy infections of Trichuris trichiura affect cognitive function in Jamaican school children. Parasitology 104, 539–547.CrossRefGoogle Scholar
Panesar, T. S. ( 1989). The moulting pattern in Trichuris muris (Nematoda: Trichuroidea). Canadian Journal of Zoology 67, 2340–2343.CrossRefGoogle Scholar
Perry, B. D., Randolph, T. F., McDermott, J. J., Sones, K. R. and Thornton, P. K. ( 2002). Investing in animal health research to alleviate poverty. ILRI (International Livestock Research Institute), Nairobi, Kenya, pp. 1–138.
Reynoldson, J. A., Behnke, J. M., Pallant, L. J., MacNish, M. G., Gilbert, F., Giles, S., Spargo, R. J. and Thompson, R. C. A. ( 1997). Failure of pyrantel in treatment of human hookworm infections (Ancylostoma duodenale) in the Kimberley region of North West Australia. Acta Tropica 68, 301–312.CrossRefGoogle Scholar
Robbins, B. H. ( 1930). A proteolytic enzyme in ficin, the anthelmintic principle of Leche de Higueron. Journal of Biological Chemistry 87, 251–257.Google Scholar
Rowan, A. D., Buttle, D. J. and Barrett, A. J. ( 1990). The cysteine proteinases of the pineapple plant. The Biochemical Journal 266, 869–875.Google Scholar
Salih, E., Malthouse, J. P. G., Kowlessur, D., Jarvis, M., O'Driscoll, M. and Brocklehurst, K. ( 1987). Differences in the chemical and catalytic characteristics of two crystallographically “identical” enzyme catalytic sites. The Biochemical Journal 247, 181–193.CrossRefGoogle Scholar
Satrija, F., Nansen, P., Bjorn, H., Murtini, S. and He, S. ( 1994). Effect of papaya latex against Ascaris suum in naturally infected pigs. Journal of Helminthology 68, 343–346.CrossRefGoogle Scholar
Satrija, F., Nansen, P., Murtini, S. and He, S. ( 1995). Anthelmintic activity of papaya latex against patent Heligmosomoides polygyrus infections in mice. Journal of Ethnopharmacology 48, 161–164.CrossRefGoogle Scholar
Soltys, J., Goyal, P. K. and Wakelin, D. ( 1999). Cellular immune responses in mice infected with the intestinal nematode Trichuris muris. Experimental Parasitology 92, 40–47.CrossRefGoogle Scholar
Stepek, G., Buttle, D. J., Duce, I. R., Lowe, A. and Behnke, J. M. ( 2005). Assessment of the anthelmintic effect of natural plant cysteine proteinases against the gastrointestinal nematode, Heligmosomoides polygyrus, in vitro. Parasitology 130, 203–211.CrossRefGoogle Scholar
Stephensen, C. B. ( 1999). Burden of infection on growth failure. Journal of Nutrition 129, 534S–538S.CrossRefGoogle Scholar
Sugiyama, S., Ohtsuki, K., Sato, K. and Kawabata, M. ( 1997). Enzymatic properties, substrate specificities and pH-activity profiles of two kiwifruit proteases. Journal of Nutritional Science and Vitaminology 43, 581–589.CrossRefGoogle Scholar
van Wyk, J. A., Malan, F. S. and Randles, J. L. ( 1997). How long before resistance makes it impossible to control some field strains of Haemonchus contortus in South Africa with any of the modern anthelmintics? Veterinary Parasitology 70, 111–122.Google Scholar
Varady, M., Praslicka, J., Corba, J. and Vesely, L. ( 1993). Multiple anthelmintic resistance of nematodes in imported goats. Veterinary Record 132, 387–388.CrossRefGoogle Scholar
Varughese, K. I., Su, Y., Cromwell, D., Hasnain, S. and Xuong, N.-H. ( 1992). Crystal structure of an actinidin-E-64 complex. Biochemistry 31, 5172–5176.CrossRefGoogle Scholar
Waller, P. J. ( 2003). The future of anthelmintics in sustainable parasite control programs for livestock. Helminthologia 40, 97–102.Google Scholar
Waruiru, R. M., Ngotho, J. W. and Mukiri, J. G. ( 1998). Multiple and multigeneric anthelmintic resistance on a sheep farm in Kenya. Tropical Animal Health and Production 30, 159–166.CrossRefGoogle Scholar
Wolstenholme, A. J., Fairweather, I., Prichard, R., von Samson-Himmelstjerna, G. and Sangster, N. C. ( 2004). Drug resistance in veterinary helminths. Trends in Parasitology 20, 469–476.CrossRefGoogle Scholar
Zucker, S., Buttle, D. J., Nicklin, M. J. H. and Barrett, A. J. ( 1985). The proteolytic activities of chymopapain, papain, and papaya proteinase III. Biochimica et Biophysica Acta 828, 196–204.CrossRefGoogle Scholar