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Objective:Aqueous extracts of Zapoteca portoricensis are used traditionally as antidiarrhea agent and in the treatment of diverse gastrointestinal disorders here in Nigeria specifically,the south part.Similarly,the a-queous extract of the plant is also used traditionally as anticonvulsant,antispasmodic and in the treatment of tonsillitis.Recently too,the anti-inflammatory and antimicrobial activities of the methanol extracts of the root of Zapoteca portoricensis was reported.In this research,we are set to investigate the trypanocidal activity of Zapoteca portoricensis.Methods:The methanol extract of the root of Zapoteca portoricensis was investigated for both in vitro and in vivo trypanocidal activity following established models.In summary,phytochemical analy-sis was carried out on both the crude powdered root and on the methanol extract following standard procedures. The oral acute toxicity test (LD50 )of the crude methanol extract was determined according to the method de-scribed by Lorke (1983).Albino mice (17g-21g)of either sex were used.The methanol extract was suspen-ded in 3 % v /v tween 85 and administered orally at doses of 10 mg/kg,100 mg/kg and 1 000 mg/kg to three groups of mice (n =3).The animals were observed for 24 hours.Based on the result obtained in this initial test,doses of 4 mg/kg,6 mg/kg,and 8 mg/kg were administered to three different mice.The LD50 was calcu-lated as the geometric mean of the lowest dose killing a mouse and the highest dose showing no death.The in-vivo /in-vitro anti-trypanosomal evaluations were carried out in experimental animals and tissue cell culture re-spectively.Results:The result of the in vitro studies shows the inhibitive concentration-50(IC-50)against Trypanosoma brucei rhodesiense (T.b.rhodesiense)to be 0.372 mg/kg,while the control drug melarsoprol was 0.006 mg/kg.On Trypanosoma brucei brucei (T .cruzi),the IC-50 is 6.42 mg/kg against 0.87 of the ref-erence drug Benznidazole.The cyctotoxicity on L-6 cells exhibited an IC-50 of 0.039 6 mg/kg against the ref-erence drug,podophyllotoxin of 0.01 mg/kg.However,the in vivo study shows that the extract,at the admin-istered doses,could not exhibit appreciable reduction of parasitemia and hence resulted to the death of test ani-mals.Conclusion:The present data suggests that Zapoteca portoricensis could yield useful leads for the devel-opment of potentially potent antitrypanocides.