Ethnopharmacological relevancePastoralists in Nigeria mix Garcinia kola seed (GK), Khaya senegalensis stem bark (KS), and Vernonia amygdalina leaves (VA) to treat leptospirosis. AimTo determine the in vitro and in vivo effect on single and combination therapy on Leptospira interrogans-infected mice. Materials and MethodsEvaluation of in vitro assay for anti-leptospiral motility of the extracts was carried out in triplicates. For the in vivo assessment, 40 adult male mice inoculated with Leptospira were randomly allocated into 8 groups of 5 mice each. Groups IV-IX were treated with 800mg/kg b.w. of KS, GK, VA, KS+GK, KS+VA, GK+VA for 5 days. Group I was negative control, II was model control, and III was treated with penicillin (3.7mg/kg b.w.) intramuscularly. ResultsIn vitro, at 90 min, all the extracts at 800, 400, and 200 mg/ml showed complete cessation of motility which was significantly (p < 0.05) different when compared to the negative control. A significant (p < 0.05) IC50 of 0.18mg/ml was recorded with GK when compared to KS (0.40mg/ml), VA (0.25mg/ml), and procaine penicillin (0.31mg/ml). Mean packed cell volume, haemoglobin concentration, and mean corpuscular haemoglobin concentration decreased significantly (p < 0.05) in all infected groups and returned to almost pre-infection values. However, significant leucocytosis (p < 0.05) was observed in group II. AST and ALP showed a significant increase (p < 0.001). Histopathological evaluation showed the extracts to prevent the distortion of normal architecture of the selected organs. ConclusionThis study demonstrates the significant potential of Garcinia kola, Khaya senegalensis, and Vernonia amygdalina extracts singly and in combination to combat leptospirosis.