Trypanocidal and cytotoxic activity of extracts of Colombian plants
Keywords:
Trypanosoma cruzi, Chagas disease, plants extracts
Abstract
Introduction. The treatment of Chagas disease is based on only two drugs with limited efficacy and significant side effects. The rich biodiversity of the Colombian flora makes bio-prospecting a potential alternative in the search for new antiparasitic drugs.
Objective. Potential trypanocidal activity and cytotoxicity was assessed in extracts from 23 Colombian plants.
Materials and methods. Extracts of leaves, stems, or of the whole plants were obtained in solvents of a range of polarities. The activity against Trypanosoma cruzi epimastigotes and the cytotoxicity were evaluated by the MTT enzymatic micro-method. Extracts active against epimastigotes and with low cytotoxicity were also tested on trypomastigotes and intracellular amastigotes.
Results. Among the extracts, biological activity was confirmed in 4 species. The extracts were active on epimastigotes and trypomastigotes; one was active also against amastigotes. The latter extract was isolated from the plant Hieronyma antioquensis and presented IC50 of 3.1 mg/ml for epimastigotes, 11.5 mg/ml for trypomastigotes and 2.9 mg/ml for amastigotes. The selectivity indexes were 25, 7, and 27 respectively.
Conclusions. The extract from H. antioquensis proved a promising candidate for Chagas disease treatment. Futhermore, the MTT enzymatic micromethod was a useful tool for screening biological activity on epimastigotes and other stages of the parasite for further extract trials.
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References
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3. Cançado JR. Criteria of Chagas disease cure. Mem Inst Oswaldo Cruz. 1999;94:331-6.
4. de Andrade LS, Zicker F, Rassi A, Rassi AG, Oliveira RM, Silva SA, et al. Early electrocardiographic abnormalities in Trypanosoma cruzi-seropositive children. Am J Trop Med Hyg. 1998;59:530-4.
5. Sosa-Estani S, Segura EL. Treatment of Trypanosoma cruzi infection in the undetermined phase. Experience and current guidelines in Argentina. Mem Inst Oswaldo Cruz. 1999:94(Suppl.1):363-5.
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7. Solari A, Ortiz S, Soto A, Arancibia C, Campillay R, Contreras M, et al. Treatment of Trypanosoma cruziinfected children with nifurtimox: A 3-year follow-up study. J Antimicrob Chemother. 2001;48:515-9.
8. Kirchhoff LV. American trypanosomiasis (Chagas' disease). En: Rakel RE, editor. Conn's current therapy. New York, USA: W.B. Saunders; 2000. p. 101-2.
9. Phillipson JD, Wright CW. Medicinal plants against protozoal diseases. Trans R Soc Trop Med Hyg.1991;85:155-65.
10. Kayser O, Kinderlen AF, Croft SL. Natural products as antiparasitic drugs. Parasitol Res. 2003;90:55-62.
11. Osorio EJ, Robledo SM, Bastida J. Alkaloids with antiprotozoal activity. Alkaloids Chem Biol. 2008;66:113-90.
12. D'Souza AJ, Schowen RL, Topp EM. Polyvinylpyrrolidonedrug conjugate: Synthesis and release mechanism. J Control Release. 2004;94:91-100.
13. Weniger B, Robledo S, Arango GJ, Deharo E, Aragon R, Muñoz V, et al. Antiprotozoal activities of Colombian plants. J Ethnopharmacol. 2001;78:193-200.
14. Maya JD, Cassels BK, Iturriaga-Vásquez P, Ferreira J, Faúndez M, Galanti N, et al. Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host. Comp Biochem Physiol A Mol Integr Physiol. 2007;146:601-20.
15. Osorio E, Arango GJ, Jiménez N, Alzate F, Ruiz G, Gutiérrez D, et al. Antiprotozoal and cytotoxic activities in vitro of Colombian Annonaceae. J Ethnopharmacol. 2007;111:630-5.
16. Atienza J, Martínez RA, Gómez A, Escario JA, Herrero A, Ochoa C, et al. Activity assays of thiadiazine derivates on Trichomonas vaginalis and amastigote forms of Trypanosoma cruzi. Chemotherapy. 1992;38:441-6.
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18. Finney JD. Statistical logic in the monitoring of reactions to therapeutic drugs. Methods Inf Med.1971;10:237-45.
19. Vieira NC, Espíndola LS, Santana JM, Veras ML, Pessoa OD, Pinheiro SM, et al. Trypanocidal activity of a new pterocarpan and other secundary metabolites of plants from northeastern Brazil flora. Bioorg Med Chem. 2008;6:1676-82.
20. Minguzzi S, Barata LES, Shin YG, Jonas PF, Chai H, Park EJ, et al. Cytotoxic withanolides from Acnistus arborescens. Phytochemistry. 2002;59:635-41.
21. Cardona D, Quiñones W, Torres F, Vélez ID, Orozco CI, Garzon J, et al. Estructura y actividad leishmanicida de larnaxolida A y B, nuevos withanólidos de Larnax glabra (Standl.) Sawyer. Actual Biol. 2005;27:81-6.
22. Leboeuf M, Cavé A, Bhaumikk PK, Mukherjee B, Mukherjee R. The phytochemistry of the Annonaceae. Phytochemistry. 1982;21:2783-813.
23. Raynaud-Le Grandic S, Fourneau C, Laurens A, Bories D, Hoquemiller R, et al. In vitro antileishmanial activity of acetogenins from Annonaceae. Biomed and Pharmacother. 2004;58:388-92.
24. Jiménez N. Contribución al estudio de la química y la actividad biológica de Annonaceae: actividad anti-leishmania de alcaloides de Rollinia pittieri y acetogeninas de Rollinia exsucca (tesis). Medellín: Universidad de Antioquia; 2005.p. 84.
25. Akinmoladun AC, Obuotor EM, Farombi EO. Evaluation of antioxidant and free radical scavenging capacities of some Nigerian indigenous medicinal plants. J Med Food. 2010;13:444-51.
26. Rojas A, Ferro E, Inchausti A, Ascurra M, Acosta N, Rodríguez E, et al. Mutagenicity, insecticidal and trypanocidal activity of some Paraguayan Asteraceae. J Ethnopharmacol. 1995;45:35-41.
27. Mallavadhani U, Anita V, Panda K, Rao YR. Pharmacology and chemotaxonomy of Diospyros. Phytochemistry. 1998;49:901-51.
28. Croft SL, Evans AT, Neal RA. The activity of plumbagin and other electron carriers against Leishmania donovani and Leishmania mexicana. Ann Trop Med Parasitol. 1985;79:651-3.
29. Campos FR, Januário AH, Rosas LV, Nascimento SK, Pereira PS, França SC, et al. Trypanocidal activity of extracts and fractions of Bertholletia excelsa. Fitoterapia. 2005;76:26-9.
30. Melo M, Ferreira L. Screening the mutagenic activities of commonly used antiparasite drugs by the simultest, a simplified Salmonella/microsome plate incorporation assay. Rev Inst Med Trop Sao Paulo. 1990;32:269-74.
31. Lacava ZG, Luna H. The anticlastogenic effect of tocopherol in peritoneal macrophages of benznidazole-treated and ovariectomized mice. Mutat Res. 1994;305:145-50.
2. Padilla JC. Situación de la enfermedad de Chagas en Colombia. Memorias. En: Guhl F, editor. Primer taller internacional sobre control de la enfermedad de Chagas. Curso de diagnóstico, manejo y tratamiento de la enfermedad de Chagas. Sexta reunión de la iniciativa andina para el control de la enfermedad de Chagas. Bogotá: Ediciones Uniandes; 2005. p. 19-24.
3. Cançado JR. Criteria of Chagas disease cure. Mem Inst Oswaldo Cruz. 1999;94:331-6.
4. de Andrade LS, Zicker F, Rassi A, Rassi AG, Oliveira RM, Silva SA, et al. Early electrocardiographic abnormalities in Trypanosoma cruzi-seropositive children. Am J Trop Med Hyg. 1998;59:530-4.
5. Sosa-Estani S, Segura EL. Treatment of Trypanosoma cruzi infection in the undetermined phase. Experience and current guidelines in Argentina. Mem Inst Oswaldo Cruz. 1999:94(Suppl.1):363-5.
6. Silveira CA, Castillo E, Castro C. Avaliação do tratamiento especifico para o Trypanosoma cruzi en criaças, na evolucion da fase indeterminada. Rev Soc Bras Med Trop. 2000;33:191-6.
7. Solari A, Ortiz S, Soto A, Arancibia C, Campillay R, Contreras M, et al. Treatment of Trypanosoma cruziinfected children with nifurtimox: A 3-year follow-up study. J Antimicrob Chemother. 2001;48:515-9.
8. Kirchhoff LV. American trypanosomiasis (Chagas' disease). En: Rakel RE, editor. Conn's current therapy. New York, USA: W.B. Saunders; 2000. p. 101-2.
9. Phillipson JD, Wright CW. Medicinal plants against protozoal diseases. Trans R Soc Trop Med Hyg.1991;85:155-65.
10. Kayser O, Kinderlen AF, Croft SL. Natural products as antiparasitic drugs. Parasitol Res. 2003;90:55-62.
11. Osorio EJ, Robledo SM, Bastida J. Alkaloids with antiprotozoal activity. Alkaloids Chem Biol. 2008;66:113-90.
12. D'Souza AJ, Schowen RL, Topp EM. Polyvinylpyrrolidonedrug conjugate: Synthesis and release mechanism. J Control Release. 2004;94:91-100.
13. Weniger B, Robledo S, Arango GJ, Deharo E, Aragon R, Muñoz V, et al. Antiprotozoal activities of Colombian plants. J Ethnopharmacol. 2001;78:193-200.
14. Maya JD, Cassels BK, Iturriaga-Vásquez P, Ferreira J, Faúndez M, Galanti N, et al. Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host. Comp Biochem Physiol A Mol Integr Physiol. 2007;146:601-20.
15. Osorio E, Arango GJ, Jiménez N, Alzate F, Ruiz G, Gutiérrez D, et al. Antiprotozoal and cytotoxic activities in vitro of Colombian Annonaceae. J Ethnopharmacol. 2007;111:630-5.
16. Atienza J, Martínez RA, Gómez A, Escario JA, Herrero A, Ochoa C, et al. Activity assays of thiadiazine derivates on Trichomonas vaginalis and amastigote forms of Trypanosoma cruzi. Chemotherapy. 1992;38:441-6.
17. Martínez RA. Variabilidad intraespecífica en Trypanosoma cruzi y ensayo de nuevos métodos para el cribado farmacológico (tesis). Madrid: Universidad Complutense de Madrid; 1996. p. 130.
18. Finney JD. Statistical logic in the monitoring of reactions to therapeutic drugs. Methods Inf Med.1971;10:237-45.
19. Vieira NC, Espíndola LS, Santana JM, Veras ML, Pessoa OD, Pinheiro SM, et al. Trypanocidal activity of a new pterocarpan and other secundary metabolites of plants from northeastern Brazil flora. Bioorg Med Chem. 2008;6:1676-82.
20. Minguzzi S, Barata LES, Shin YG, Jonas PF, Chai H, Park EJ, et al. Cytotoxic withanolides from Acnistus arborescens. Phytochemistry. 2002;59:635-41.
21. Cardona D, Quiñones W, Torres F, Vélez ID, Orozco CI, Garzon J, et al. Estructura y actividad leishmanicida de larnaxolida A y B, nuevos withanólidos de Larnax glabra (Standl.) Sawyer. Actual Biol. 2005;27:81-6.
22. Leboeuf M, Cavé A, Bhaumikk PK, Mukherjee B, Mukherjee R. The phytochemistry of the Annonaceae. Phytochemistry. 1982;21:2783-813.
23. Raynaud-Le Grandic S, Fourneau C, Laurens A, Bories D, Hoquemiller R, et al. In vitro antileishmanial activity of acetogenins from Annonaceae. Biomed and Pharmacother. 2004;58:388-92.
24. Jiménez N. Contribución al estudio de la química y la actividad biológica de Annonaceae: actividad anti-leishmania de alcaloides de Rollinia pittieri y acetogeninas de Rollinia exsucca (tesis). Medellín: Universidad de Antioquia; 2005.p. 84.
25. Akinmoladun AC, Obuotor EM, Farombi EO. Evaluation of antioxidant and free radical scavenging capacities of some Nigerian indigenous medicinal plants. J Med Food. 2010;13:444-51.
26. Rojas A, Ferro E, Inchausti A, Ascurra M, Acosta N, Rodríguez E, et al. Mutagenicity, insecticidal and trypanocidal activity of some Paraguayan Asteraceae. J Ethnopharmacol. 1995;45:35-41.
27. Mallavadhani U, Anita V, Panda K, Rao YR. Pharmacology and chemotaxonomy of Diospyros. Phytochemistry. 1998;49:901-51.
28. Croft SL, Evans AT, Neal RA. The activity of plumbagin and other electron carriers against Leishmania donovani and Leishmania mexicana. Ann Trop Med Parasitol. 1985;79:651-3.
29. Campos FR, Januário AH, Rosas LV, Nascimento SK, Pereira PS, França SC, et al. Trypanocidal activity of extracts and fractions of Bertholletia excelsa. Fitoterapia. 2005;76:26-9.
30. Melo M, Ferreira L. Screening the mutagenic activities of commonly used antiparasite drugs by the simultest, a simplified Salmonella/microsome plate incorporation assay. Rev Inst Med Trop Sao Paulo. 1990;32:269-74.
31. Lacava ZG, Luna H. The anticlastogenic effect of tocopherol in peritoneal macrophages of benznidazole-treated and ovariectomized mice. Mutat Res. 1994;305:145-50.
How to Cite
1.
Valencia L, Muñoz DL, Robledo SM, Echeverri F, Arango GJ, Vélez ID, et al. Trypanocidal and cytotoxic activity of extracts of Colombian plants. biomedica [Internet]. 2011 Jun. 30 [cited 2024 May 11];31(4):552-9. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/426
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