Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-23T23:06:30.494Z Has data issue: false hasContentIssue false
  • English
  • Français

Applicability of plant-based products in the treatment of Trypanosoma cruzi and Trypanosoma brucei infections: a systematic review of preclinical in vivo evidence

Published online by Cambridge University Press:  05 June 2017

RODRIGO M. PEREIRA ,
GLÍCIA M. Z. GRECO ,
ANDREIA M. MOREIRA ,
PABLO F. CHAGAS ,
IVO S. CALDAS ,
REGGIANI V. GONÇALVES  and
RÔMULO D. NOVAES
RODRIGO M. PEREIRA
Affiliation:
Institute of Biomedical Sciences, Federal University of Alfenas, 37130-001, Minas Gerais, Brazil Postgraduate Program in Biosciences Applied to Health, Federal University of Alfenas, 37130-001, Minas Gerais, Brazil
GLÍCIA M. Z. GRECO
Affiliation:
Institute of Biomedical Sciences, Federal University of Alfenas, 37130-001, Minas Gerais, Brazil Postgraduate Program in Biosciences Applied to Health, Federal University of Alfenas, 37130-001, Minas Gerais, Brazil
ANDREIA M. MOREIRA
Affiliation:
Institute of Biomedical Sciences, Federal University of Alfenas, 37130-001, Minas Gerais, Brazil Postgraduate Program in Biosciences Applied to Health, Federal University of Alfenas, 37130-001, Minas Gerais, Brazil
PABLO F. CHAGAS
Affiliation:
Institute of Biomedical Sciences, Federal University of Alfenas, 37130-001, Minas Gerais, Brazil Postgraduate Program in Biological Sciences, Federal University of Alfenas, 37130–001, Minas Gerais, Brazil
IVO S. CALDAS
Affiliation:
Institute of Biomedical Sciences, Federal University of Alfenas, 37130-001, Minas Gerais, Brazil
REGGIANI V. GONÇALVES
Affiliation:
Department of Animal Biology, Federal University of Viçosa, 36570-000, Minas Gerais, Brazil
RÔMULO D. NOVAES*
Affiliation:
Institute of Biomedical Sciences, Federal University of Alfenas, 37130-001, Minas Gerais, Brazil
*
*Corresponding author: Institute of Biomedical Sciences, Department of Structural Biology, Federal University of Alfenas, Rua Gabriel Monteiro da Silva, 700, Alfenas, 37130-001, Minas Gerais, Brazil. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Chagas disease and sleeping sickness are neglected tropical diseases closely related to poverty, for which the development of plant-derived treatments has not been a promising prospect. Thus, we systematicaly review the preclinical in vivo evidence on the applicability of plant-based products in the treatment of Trypanosoma cruzi and Trypanosoma brucei infections. Characteristics such as disease models, treatments, toxicological safety and methodological bias were analysed. We recovered 66 full text articles from 16 countries investigating 91 plant species. The disease models and treatments were highly variable. Most studies used native (n = 36, 54·54%) or exotic (n = 30, 45·46%) plants with ethnodirected indication (n = 45, 68·18%) for trypanosomiasis treatment. Complete phytochemical screening and toxicity assays were reported in only 15 (22·73%) and 32 (48·49%) studies, respectively. The currently available preclinical evidence is at high risk of bias. The absence of or incomplete characterization of animal models, treatment protocols, and phytochemical/toxicity analyses impaired the internal validity of the individual studies. Contradictory results of a same plant species compromise the external validity of the evidence, making it difficult determine the effectiveness, safety and biotechnological potential of plant-derived products in the development of new anti-infective agents to treat T. cruzi and T. brucei infections.

Keywords

Experimental therapeuticshuman trypanosomiasisneglected diseasesparasitic diseasesparasitology
Type
Review Article
Information
Parasitology , Volume 144 , Issue 10 , September 2017 , pp. 1275 - 1287
Check for updates
Copyright
Copyright © Cambridge University Press 2017 

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

Adamu, M., Nwosu, C. O. and Agbede, R. I. S. (2009). Anti-trypanosomal effects of aqueous extract of Ocimum gratissimum (lamiaceae) leaf in rats infected with Trypanosoma brucei brucei . African Journal of Traditional, Complementary and Alternative Medicines 6(3), 262–267.Google Scholar
Adelodun, V. O., Elusiyan, C. A., Olorunmola, F. O., Adewoyin, F. B., Omisore, N. O., Adepiti, A. O., Agbedahunsi, J. M. and Adewunmi, C. O. (2013). Evaluation of antitrypanosomal and anti inflammatory activities of selected Nigerian medicinal plants in mice. African Journal of Traditional, Complementary and Alternative Medicines 10(6), 469–476.Google Scholar
Aderbauer, B., Clausen, P. H., Kershaw, O. and Melzig, M. F. (2008). In vitro and in vivo trypanocidal effect of lipophilic extracts of medicinal plants from Mali and Burkina Faso. Journal of Ethnopharmacology 119(2), 225–231.Google Scholar
Ajazuddin, and Saraf, S. (2010). Applications of novel drug delivery system for herbal formulations. Fitoterapia 81(7), 680–689.Google Scholar
Amrouni, D., Meiller, A., Gautier-Sauvigné, S., Piraud, M, Bouteille, B., Vincendeau, P., Buguet, A. and Cespuglio, R. (2011). Cerebral changes occurring in arginase and dimethylarginine dimethylaminohydrolase (DDAH) in a rat model of sleeping sickness. PLoS ONE 6(3), e16891.Google Scholar
Andrade, D. V., Gollob, K. J. and Dutra, W. O. (2014). Acute Chagas disease: new global challenges for an old neglected disease. PLoS neglected tropical diseases 8(7), 1–10.Google Scholar
Andrade, L. O., Machado, C. R., Chiari, E., Pena, S. D. and Macedo, A. M. (2002). Trypanosoma cruzi: role of host genetic background in the differential tissue distribution of parasite clonal populations. Experimental Parasitology 100(4), 269–275.Google Scholar
Antia, R. E., Olayemi, J. O., Aina, O. O. and Ajaiyeoba, E. O. (2009). In vitro and in vivo animal model antitrypanosomal evaluation of ten medicinal plant extracts from south west Nigeria. African Journal of Biotechnology 8(8), 1437–1440.Google Scholar
Antoine-Moussiaux, N., Magez, S. and Desmecht, D. (2008). Contributions of experimental mouse models to the understanding of African trypanosomiasis. Trends in Parasitology 24(9), 411–418.Google Scholar
Atanasov, A. G., Waltenberger, B., Pferschy-Wenzig, E. M., Linder, T., Wawrosch, C., Uhrin, P., Temml, V., Wang, L., Schwaiger, S., Heiss, E. H., Rollinger, J. M., Schuster, D., Breuss, J. M., Bochkov, V., Mihovilovic, M. D., Kopp, B., Bauer, R., Dirsch, V. M. and Stuppner, H. (2015). Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnology Advances 33(8), 1582–1614.Google Scholar
Avery, V. (2013). Ask the experts: drug discovery for the treatment of leishmaniasis, African sleeping sickness and Chagas disease. Future Medicinal Chemistry 5(15), 1709–1718.Google Scholar
Ayyari, M., Salehi, P., Ebrahimi, S. N., Zimmermann, S., Portmann, L., Krauth-Siegel, R. L., Kaiser, M., Brun, R., Rezadoost, H., Rezazadeh, S. and Hamburger, M. (2014). Antitrypanosomal isothiocyanate and thiocarbamate glycosides from Moringa peregrina . Planta Medica 80(1), 86–89.Google Scholar
Bastos, J. K., Albuquerque, S. and Silva, M. L. (1999). Evaluation of the trypanocidal activity of lignans isolated from the leaves of Zanthoxylum naranjillo . Planta Medica 65(6), 541–544.Google Scholar
Bern, C. (2015). Chagas’ disease. New England Journal of Medicine 373(5), 456–466.Google Scholar
Bhattaram, V. A., Graefe, U., Kohlert, C., Veit, M. and Derendorf, H. (2002). Pharmacokinetics and bioavailability of herbal medicinal products. Phytomedicine 9, 1–33.Google Scholar
Bocchi, E. A. (2013). Heart in South America. Current Cardiology Reviews 9(2), 147–156.CrossRefGoogle ScholarPubMed
Boelaert, M., Meheus, F., Robays, J. and Lutumba, P. (2010). Socio-economic aspects of neglected diseases: sleeping sickness and visceral leishmaniasis. Annals of Tropical Medicine and Parasitology 104(7), 535–542.Google Scholar
Boldizsar, F., Mikecz, K. and Glant, T. T. (2010). Immunosenescence and its potential modulation: lessons from mouse models. Expert Review of Clinical Immunology 6(3), 353–357.Google Scholar
Cáceres, A., López, B., González, S., Berger, I., Tada, I. and Maki, J. (1998). Plants used in Guatemala for the treatment of protozoal infections. I. Screening of activity to bacteria, fungi and American trypanosomes of 13 native plants. Journal of Ethnopharmacology 62(3), 195–202.Google Scholar
Calixto, J. B. (2000). Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents). Brazilian Journal of Medical and Biological Research 33(2), 179–189.Google Scholar
Cançado, J. R. (1999). Criteria of Chagas disease cure. Memórias do Instituto Oswaldo Cruz 94(S1), 331–335.Google Scholar
Cançado, J. R. (2002). Long term evaluation of etiological treatment of Chagas disease with benznidazole. Revista do Instituto de Medicina Tropical de Sao Paulo 44(1), 29–37.CrossRefGoogle ScholarPubMed
Carvalho, C. M. E., Andrade, M. C., Xavier, S. S., Mangia, R. H., Britto, C. C., Jansen, A. M., Fernandes, O., Lannes-Vieira, J. and Bonecini-Almeida, M. G. (2003). Chronic Chagas’ disease in rhesus monkeys (Macaca mulatta): evaluation of parasitemia, serology, electrocardiography, echocardiography, and radiology. American Journal of Tropical Medicine and Hygiene 68(6), 683–691.Google Scholar
Chevrier, C., Canini, F., Darsaud, A., Cespuglio, R., Buguet, A. and Bourdon, L. (2005). Clinical assessment of the entry into neurological state in rat experimental African trypanosomiasis. Acta Tropica 95(1), 33–39.CrossRefGoogle Scholar
Clayton, J. A. and Collins, F. S. (2014). Policy: NIH to balance sex in cell and animal studies. Nature 509(7500), 282–283.Google Scholar
da Rocha, C. Q., Queiroz, E. F., Meira, C. S., Moreira, D. R., Soares, M. B., Marcourt, L., Vilegas, W. and Wolfender, J. L. (2014). Dimeric flavonoids from Arrabidaea brachypoda and assessment of their anti-Trypanosoma cruzi activity. Journal of Natural Products 77(6), 1345–1350.Google Scholar
Darsaud, A., Bourdon, L., Chevrier, C., Keita, M., Bouteille, B., Queyroy, A., Canini, F., Cespuglio, R., Dumas, M. and Buguet, A. (2003). Clinical follow-up in the rat experimental model of African trypanosomiasis. Experimental Biology and Medicine 228(11), 1355–1362.Google Scholar
Deborggraeve, S., Koffi, M., Jamonneau, V., Bonsu, F. A., Queyson, R., Simarro, P. P., Herdewijn, P. and Büscher, P. (2008). Molecular analysis of archived blood slides reveals an atypical human Trypanosoma infection. Diagnostic Microbiology and Infectious Disease 61(4), 428–433.Google Scholar
de Menezes, V. T., Queiroz, A. O., Gomes, M. A., Marques, M. A. and Jansen, A. M. (2004). Trypanosoma evansi in inbred and Swiss–Webster mice: distinct aspects of pathogenesis. Parasitology Research 94(3), 193–200.Google Scholar
De Smet, P. A. and Brouwers, J. R. (1997). Pharmacokinetic evaluation of Herbal remedies. Clinical Pharmacokinetics 32(6), 427–436.Google Scholar
Dias, J. C. P. et al. (2016). Brazilian consensus on Chagas disease, 2015. Epidemiologia e Serviços de Saúde 25(esp), 7–86.Google Scholar
Ekins, S., Williams, A. J., Krasowski, M. D. and Freundlich, J. S. (2011). In silico repositioning of approved drugs for rare and neglected diseases. Drug Discovery Today 16(7–8), 298–310.Google Scholar
Ekor, M. (2014). The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Frontiers in Pharmacology 4, 177.Google Scholar
Enanga, B., Burchmore, R. J., Stewart, M. L. and Barrett, M. P. (2002). Sleeping sickness and the brain. Cellular and Molecular Life Sciences 59(5), 845–858.Google Scholar
Ferreira, M. E., Cebrián-Torrejón, G., Corrales, A. S., Vera de Bilbao, N., Rolón, M., Gomez, C. V., Leblanc, K., Yaluf, G., Schinini, A., Torres, S., Serna, E., Rojas de Arias, A., Poupon, E. and Fournet, A. (2011). Zanthoxylum chiloperone leaves extract: first sustainable Chagas disease treatment. Journal of Ethnopharmacology 133(3), 986–993.Google Scholar
Festing, M. F. (1999). Warning: the use of heterogeneous mice may seriously damage your research. Neurobiology of Aging 20(2), 237–244.Google Scholar
Festing, M. F. W. (2016). Genetically defined strains in drug development and toxicity testing. Methods in Molecular Biology 1438, 1–17.Google Scholar
Giordani, F., Morrison, L. J., Rowan, T. G., de Koning, H. P. and Barrett, M. P. (2016). The animal trypanosomiases and their chemotherapy: a review. Parasitology 143(14), 1862–1889.Google Scholar
Goupil, L. S. and McKerrow, J. H. (2014). Introduction: drug discovery and development for neglected diseases. Chemical Reviews 114(22), 11131–11137.Google Scholar
Guedes, P. M., Veloso, V. M., Tafuri, W. L., Galvão, L. M., Carneiro, C. M., Lana, Md., Chiari, E., Ataide Soares, K. and Bahia, M. T. (2002). The dog as model for chemotherapy of the Chagas’ disease. Acta Tropica 84(1), 9–17.Google Scholar
Guzman-Marin, E., Jimenez-Coello, M., Puerto-Solis, M., Ortega-Pacheco, A. and Acosta-Viana, K. Y. (2012). Influence of Triatoma dimidiata in modulating the virulence of Trypanosoma cruzi Mexican strains. Interdisciplinary Perspectives on Infectious Diseases 2012, 328091.Google Scholar
Harvey, A. L. (2008). Natural products in drug discovery. Drug Discovery Today 13(19–20), 894–901.Google Scholar
Hasiwa, N., Bailey, J., Clausing, P., Daneshian, M., Eileraas, M., Farkas, S., Gyertyán, I., Hubrecht, R., Kobel, W., Krummenacher, G., Leist, M., Lohi, H., Miklósi, A., Ohl, F., Olejniczak, K., Schmitt, G., Sinnett-Smith, P., Smith, D., Wagner, K., Yager, J. D., Zurlo, J. and Hartung, T. (2011). Critical evaluation of the use of dogs in biomedical research and testing in Europe. Alternatives to Animal Experimentation 28(4), 326–340.Google Scholar
Hedley, L., Fink, D., Sparkes, D. and Chiodini, P. L. (2016). African sleeping sickness. British Journal of Hospital Medicine 77(Sup10), C157–C160.Google Scholar
Heinrich, M. and Gibbons, S. (2001). Ethnopharmacology in drug discovery: an analysis of its role and potential contribution. Journal of Pharmacy and Pharmacology 53(4), 425–432.Google Scholar
Hertweck, C. (2015). Natural products as source of therapeutics against parasitic diseases. Angewandte Chemie International Edition 54(49), 14622–14624.Google Scholar
Hooijmans, C. R. and Ritskes-Hoitinga, M. (2013). Progress in using systematic reviews of animal studies to improve translational research. PLoS Medicine 10(7), 1–4.Google Scholar
Hooijmans, C. R., Tillema, A., Leenaars, M. and Ritskes-Hoitinga, M. (2010). Enhancing search efficiency by means of a search filter for finding all studies on animal experimentation in PubMed. Laboratory Animals 44(3), 170–175.Google Scholar
Ibrahim, M. A., Njoku, G. C. and Sallau, A. B. (2008). In vivo activity of stem bark aqueous extract of Khaya senegalensis against Trypanosoma brucei . African Journal of Biotechnology 7(5), 661–663.Google Scholar
Ibrahim, M. A., Musa, A. M., Aliyu, A. B., Mayaki, H. S., Gideon, A. and Islam, M. S. (2013 a). Phenolics-rich fraction of Khaya senegalensis stem bark: antitrypanosomal activity and amelioration of some parasite-induced pathological changes. Pharmaceutical Biology 51(7), 906–913.Google Scholar
Ibrahim, M. A., Aliyu, A. B., Abdullahi, H., Solomon, T., Toko, E., Garba, A., Bashir, M. and Habila, N. (2013 b). Lactone-rich fraction from Vernonia blumeoides: antitrypanosomal activity and alleviation of the parasite-induced anemia and organ damage. Journal Natural Medicines 67(4), 750–757.Google Scholar
Jiménez-Coello, M., Acosta-Viana, K. Y., Pérez, G. M. S. and Guzmán-Marín Edel, S. (2011). In vivo activity of (8-hydroxymethylen)-trieicosanyl acetate against Trypanosoma cruzi during acute phase of the infection. African Journal of Traditional, Complementary and Alternative Medicines 8(4), 198–207.Google Scholar
Jiménez-Coello, M., Acosta-Viana, K. Y., Ortega-Pacheco, A., Perez-Gutierrez, S. and Guzman-Marin, E. (2014). In-vivo antiprotozoal activity of the chloroform extract from Carica papaya seeds against amastigote stage of Trypanosoma cruzi during indeterminate and chronic phase of infection. Evidence-Based Complementary and Alternative Medicine 2014, 1–7.Google Scholar
Keita, M., Bouteille, B., Enanga, B., Vallat, J. M. and Dumas, M. (1997). Trypanosoma brucei brucei: a long-term model of human African trypanosomiasis in mice, meningo-encephalitis, astrocytosis, and neurological disorders. Experimental Parasitolology 85(2), 183–192.Google Scholar
Kennedy, P. G. E. (2013). Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness). Lancet Neurology 12(2), 186–194.Google Scholar
Kesarwani, K., Gupta, R. and Mukerjee, A. (2013). Bioavailability enhancers of herbal origin: an overview. Asian Pacific Journal of Tropical Biomedicine 3(4), 253–266.Google Scholar
Kubata, B. K., Nagamune, K., Murakami, N., Merkel, P., Kabututu, Z., Martin, S. K., Kalulu, T. M., Huq, M., Yoshida, M., Ohnishi-Kameyama, M., Kinoshita, T., Duszenko, M. and Urade, Y. (2005). Kola acuminata proanthocyanidins: a class of anti-trypanosomal compounds effective against Trypanosoma brucei . International Journal of Parasitology 35(1), 91–103.Google Scholar
León, C. M., Montilla, M., Vanegas, R., Castillo, M., Parra, E. and Ramírez, J. D. (2017). Murine models susceptibility to distinct Trypanosoma cruzi I genotypes infection. Parasitology 144(4), 512–519.Google Scholar
Lozano, E., Strauss, M., Spina, R., Cifuente, D., Tonn, C., Rivarola, H. W. and Sosa, M. A. (2016). The in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from Salvia gilliesii . Parasitology International 65(1), 23–26.CrossRefGoogle ScholarPubMed
Machado, F. S., Dutra, W. O., Esper, L., Gollob, K. J., Teixeira, M. M., Factor, S. M., Weiss, L. M., Nagajyothi, F., Tanowitz, H. B. and Garg, N. J. (2012). Current understanding of immunity to Trypanosoma cruzi infection and pathogenesis of Chagas disease. Seminars in Immunopathology 34(6), 753–770.Google Scholar
Mann, A., Ifarajimi, O. R., Adewoye, A. T., Ukam, C., Udeme, E. E., Okorie, I. I., Sakpe, M. S., Ibrahim, D. R., Yahaya, Y. A., Kabir, A. Y. and Ogbadoyi, E. O. (2011). In vivo antitrypanosomal effects of some ethnomedicinal plants from Nupeland of north central Nigeria. African Journal of Traditional, Complementary and Alternative Medicines 8(1), 15–21.Google Scholar
Marcus, D. M. and Snodgrass, W. R. (2005). Do no harm: avoidance of herbal medicines during pregnancy. Obstetrics & Gynecology 105(5, Part 1), 1119–1122.Google Scholar
Marín, C., Ramírez-Macías, I., López-Céspedes, A., Olmo, F., Villegas, N., Díaz, J. G., Rosales, M. J., Gutiérrez-Sánchez, R. and Sánchez-Moreno, M. (2011). In vitro and in vivo trypanocidal activity of flavonoids from Delphinium staphisagria against Chagas disease. Journal of Natural Products 74(4), 744–750.Google Scholar
Marin-Neto, J. A., Cunha-Neto, E., Maciel, B. C. and Simões, M. V. (2007). Pathogenesis of chronic Chagas heart disease. Circulation 115(9), 1109–1123.Google Scholar
Martínez-Díaz, R. A., Escario, J. A., Nogal-Ruiz, J. J. and Gómez-Barrio, A. (2001). Biological characterization of Trypanosoma cruzi strains. Memorias do Instuto Oswaldo Cruz 96(1), 53–59.CrossRefGoogle ScholarPubMed
Mbaya, A. W., Nwosu, C. O. and Onyeyili, P. A. (2007). Toxicity and anti-trypanosomal effects of ethanolic extract of Butyrospermum paradoxum (Sapotaceae) stem bark in rats infected with Trypanosoma brucei and Trypanosoma congolense . Journal of Ethnopharmacology 111(3), 526–530.Google Scholar
McGrath, J. C. and Lilley, E. (2015). Implementing guidelines on reporting research using animals (ARRIVE): new requirements for publication in BJP. British Journal of Pharmacology 172(13), 3189–3193.Google Scholar
Meira, C. S., Guimarães, E. T., Dos Santos, J. A., Moreira, D. R., Nogueira, R. C., Tomassini, T. C., Ribeiro, I. M., de Souza, C. V., Ribeiro Dos Santos, R. and Soares, M. B. (2015). In vitro and in vivo antiparasitic activity of Physalis angulata L. concentrated ethanolic extract against Trypanosoma cruzi . Phytomedicine 22(11), 969–974.Google Scholar
Melo, R. C. and Machado, C. R. (2001). Trypanosoma cruzi: peripheral blood monocytes and heart macrophages in the resistance to acute experimental infection in rats. Experimental Parasitology 97(1), 15–23.Google Scholar
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G. and PRISMA Group. (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Medicine 6(7), e1000097.Google Scholar
Muller, P. Y. and Milton, M. N. (2012). The determination and interpretation of the therapeutic index in drug development. Nature Reviews Drug Discovery 11(10), 751–761.Google Scholar
Murray, M., Morrison, W. I. and Whitelaw, D. D. (1982). Host susceptibility to African trypanosomiasis: trypanotolerance. Advances in Parasitology 21, 1–68.Google Scholar
Nasimolo, J., Kiama, S. G., Gathumbi, P. K., Makanya, A. N. and Kagira, J. M. (2014). Erythrina abyssinica prevents meningoencephalitis in chronic Trypanosoma brucei brucei mouse model. Metabolic Brain Disease 29(2), 509–519.Google Scholar
Ndjonka, D., Rapado, L. N., Silber, A. M., Liebau, E. and Wrenger, C. (2013). Natural products as a source for treating neglected parasitic diseases. International Journal of Molecular Sciences 14(2), 3395–3439.Google Scholar
Novaes, R. D., Gonçalves, R. V., Penitente, A. R., Bozi, L. H., Neves, C. A., Maldonado, I. R., Natali, A. J. and Talvani, A. (2016). Modulation of inflammatory and oxidative status by exercise attenuates cardiac morphofunctional remodeling in experimental Chagas cardiomyopathy. Life Sciences 152, 210–219.Google Scholar
Olliaro, P. L., Kuesel, A. C. and Reeder, J. C. (2015). A changing model for developing health products for poverty-related infectious diseases. PLoS neglected Tropical Diseases 9(1), 9–11.CrossRefGoogle ScholarPubMed
Olukunle, J. O., Abatan, M. O., Soniran, O. T., Takeet, M. I., Idowu, O. A., Akande, F. A., Biobaku, K. T. and Jacobs, E. B. (2010). In vivo antitrypanosomal evaluation of five medicinal plant extracts from Ogun State, Nigeria. Scientific World Journal 5(1), 17–19.Google Scholar
Pan, S. Y., Zhou, S. F., Gao, S. H., Yu, Z. L., Zhang, S. F., Tang, M. K., Sun, J. N., Ma, D. L., Han, Y. F., Fong, W. F. and Ko, K. M. (2013). New perspectives on how to discover drugs from herbal medicines: CAM'S outstanding contribution to modern therapeutics. Evidence-based Complementary and Alternative Medicine 2013, 627375.Google Scholar
Parasuraman, S. (2011). Toxicological screening. Journal of Pharmacology and Pharmacotherapeutics 2(2), 74–79.Google Scholar
Pritchard, J. F., Jurima-Romet, M, Reimer, M. L, Mortimer, E., Rolfe, B. and Cayen, M. N. (2003). Making better drugs: decision gates in non-clinical drug development. Nature Reviews Drug Discovery 2(7), 542–553.Google Scholar
Ramesha, B. T., Gertsch, J., Ravikanth, G., Priti, V., Ganeshaiah, K. N. and Uma Shaanker, R. (2011). Biodiversity and chemodiversity: future perspectives in bioprospecting. Current Drug Targets 12, 1515–1530.Google Scholar
Ramírez-Macías, I., Marín, C., Chahboun, R., Messouri, I., Olmo, F., Rosales, M. J., Gutierrez-Sánchez, R., Alvarez-Manzaneda, E. and Sánchez-Moreno, M. (2012). In vitro and in vivo studies of the trypanocidal activity of four terpenoid derivatives against Trypanosoma cruzi . American Journal of Tropical Medicine and Hygiene 87(3), 481–488.Google Scholar
Rivera-Vanderpas, M. T., Rodriguez, A. M., Afchain, D., Bazin, H. and Capron, A. (1983). Trypanosoma cruzi: variation in susceptibility of inbred strains of rats. Acta Tropica 40(1), 5–10.Google Scholar
Salem, M. M. and Werbovetz, K. (2006). Natural products from plants as drug candidates and lead compounds against leishmaniasis and trypanosomiasis. Current Medicinal Chemistry 13(21), 2571–2598.Google Scholar
Santos, E. C., Novaes, R. D., Cupertino, M. C., Bastos, D. S., Klein, R. C., Silva, E. A., Fietto, J. L., Talvani, A., Bahia, M. T. and Oliveira, L. L. (2015). Concomitant benznidazole and suramin chemotherapy in mice infected with a virulent strain of Trypanosoma cruzi . Antimicrobials Agents and Chemotherapy 59(10), 5999–6006.Google Scholar
Schmidt, T. J., Khalid, S. A., Romanha, A. J., Alves, T. M., Biavatti, M. W., Brun, R., Da Costa, F. B., de Castro, S. L., Ferreira, V. F., de Lacerda, M. V., Lago, J. H., Leon, L. L., Lopes, N. P., das Neves Amorim, R. C., Niehues, M., Ogungbe, I. V., Pohlit, A. M., Scotti, M. T., Setzer, W. N., de N C Soeiro, M., Steindel, M. and Tempone, A. G. (2012). The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases – Part II. Current Medicinal Chemistry 19(14), 2176–2228.Google Scholar
Schuster, J. P. and Schaub, G. A. (2001). Trypanosoma cruzi: the development of estrus cycle and parasitemia in female mice maintained with or without male pheromones. Parasitology Research 87(12), 985–993.Google Scholar
Shearer, G. M. (1997). Th1/Th2 changes in aging. Mechanisms of Ageing and Development 94(1–3), 1–5.Google ScholarPubMed
Silva, Fdos S., Albuquerque, U. P., Costa Júnior, L. M., Lima, Ada. S., do Nascimento, A. L. and Monteiro, J. M. (2014). An ethnopharmacological assessment of the use of plants against parasitic diseases in humans and animals. Journal of Ethnopharmacology 155(2), 1332–1341.Google Scholar
Staub, P. O., Geck, M. S., Weckerle, C. S., Casu, L. and Leonti, M. (2015). Classifying diseases and remedies in ethnomedicine and ethnopharmacology. Journal of Ethnopharmacology 174, 514–519.Google Scholar
Sudarshi, D. and Brown, M. (2015). Human African trypanosomiasis in non-endemic countries. Clinical Medicine 15(1), 70–73.Google Scholar
Sülsen, V. P., Frank, F. M., Cazorla, S. I., Anesini, C. A., Malchiodi, E. L., Freixa, B., Vila, R., Muschietti, L. V. and Martino, V. S. (2008). Trypanocidal and leishmanicidal activities of sesquiterpene lactones from Ambrosia tenuifolia Sprengel (Asteraceae). Antimicrobials Agents and Chemotherapy 52(7), 2415–2419.Google Scholar
Sülsen, V. P., Frank, F. M., Cazorla, S. I., Barrera, P., Freixa, B., Vila, R., Sosa, M. A, Malchiodi, E. L., Muschietti, L. V. and Martino, V. S. (2011). Psilostachyin C: a natural compound with trypanocidal activity. International Journal of Antimicrobials Agents 37(6), 536–543.Google Scholar
Urbina, J. A. (2010). Specific chemotherapy of Chagas disease: relevance, current limitations and new approaches. Acta Tropica 115(1–2), 55–68.Google Scholar
van Agtmael, M. A., Eggelte, T. A. and van Boxtel, C. J. (1999). Artemisinin drugs in the treatment of malaria: from medicinal herb to registered medication. Trends in Pharmacological Sciences 20(5), 199–205.Google Scholar
Van Luijk, J., Bakker, B., Rovers, M. M., Ritskes-Hoitinga, M., de Vries, R. B. and Leenaars, M. (2014). Systematic reviews of animal studies; missing link in translational research? PLoS ONE 9(3), 1–5.Google Scholar
Varela, J., Serna, E., Torres, S., Yaluff, G., de Bilbao, N. I., Miño, P., Chiriboga, X., Cerecetto, H. and González, M. (2014). In vivo anti-Trypanosoma cruzi activity of hydro-ethanolic extract and isolated active principles from Aristeguietia glutinosa and mechanism of action studies. Molecules 19(6), 8488–8502.Google Scholar
Vincendeau, P. and Bouteille, B. (2006). Immunology and immunopathology of African trypanosomiasis. Anais da Academia Brasileira de Ciências 78(4), 645–665.Google Scholar
Welburn, S. C., Fèvre, E. M., Coleman, P. G., Odiit, M. and Maudlin, I. (2001). Sleeping sickness: a tale of two diseases. Trends in Parasitology 17(1), 19–24.Google Scholar
Youan, B. B. C., Coulibaly, S., Miezan, T. B., Doua, F. and Bamba, M. (1997). In vivo evaluation of sixteen plant extracts on mice inoculated with Trypanosoma brucei gambiense . Bulletin of the World Health Organization 75(4), 343–348.Google Scholar
WHO, World Health Organization. (2016 a). Chagas disease (American trypanosomiasis). Updated March 2016. http://www.who.int/mediacentre/factsheets/fs340/en/ Google Scholar
WHO, World Health Organization. (2016 b). Trypanosomiasis, human African (sleeping sickness). Updated February 2016. http://www.who.int/mediacentre/factsheets/fs259/en/ Google Scholar

Pereira supplementary material

Pereira supplementary material

Download Pereira supplementary material(Audio)
Audio 212 KB