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Thus, we systematicaly review the preclinical<jats:italic>in vivo<\/jats:italic>evidence on the applicability of plant-based products in the treatment of<jats:italic>Trypanosoma cruzi<\/jats:italic>and<jats:italic>Trypanosoma brucei<\/jats:italic>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 (<jats:italic>n<\/jats:italic>= 36, 54\u00b754%) or exotic (<jats:italic>n<\/jats:italic>= 30, 45\u00b746%) plants with ethnodirected indication (<jats:italic>n<\/jats:italic>= 45, 68\u00b718%) for trypanosomiasis treatment. Complete phytochemical screening and toxicity assays were reported in only 15 (22\u00b773%) and 32 (48\u00b749%) 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<jats:italic>T. cruzi<\/jats:italic>and<jats:italic>T. brucei<\/jats:italic>infections.<\/jats:p>","DOI":"10.1017\/s0031182017000634","type":"journal-article","created":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T07:56:46Z","timestamp":1496649406000},"page":"1275-1287","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":38,"title":["Applicability of plant-based products in the treatment of<i>Trypanosoma cruzi<\/i>and<i>Trypanosoma brucei<\/i>infections: a systematic review of preclinical<i>in vivo<\/i>evidence"],"prefix":"10.1017","volume":"144","author":[{"given":"RODRIGO M.","family":"PEREIRA","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GL\u00cdCIA M. 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