Antagonistic antimalarial properties of pawpaw leaf aqueous extract in combination with artesunic acid in Plasmodium berghei-infected mice

Background & objectives: Artemisinins, the main stay in the treatment of malaria are used in combinationswith other antimalarials to forestall resistance, as artemisinin-combination therapies (ACTs). However, ACTsare expensive and some of the non-artemisinin components are not well-tolerated by patients. There areseveral folkloric and scientific proofs of the efficacy of herbal remedies for malaria. Mature leaves of Caricapapaya is widely used to treat malaria in several African countries. An ACT involving a medicinal herb extractor its active constituent(s) will provide an indigenous alternative/herbal ACT.Methods: Mature fresh leaves of Carica papaya were grounded and macerated in cold distilled water for 24 hand the extract (PCE) was stored in the refrigerator for seven days. Fresh extracts were made as needed. Theantiplasmodial activity of PCE and/or artesunic acid were determined by using the Peter’s 4-day suppressivetest in Plasmodium berghei-infected mice. The ED50 and ED90 were calculated from the dose-responserelationships.Results: The combination of 50 mg/kg of PCE and 15 mg/kg of artesunic acid produced a significant reductionof parasitemia (81.25%), compared to 50 mg/kg PCE alone (37.7%). The mean survival time of the combinationsof PCE and 15 mg/kg of artesunic acid, and PCE alone followed a dose-dependent manner. The ED50 of PCEshowed that it has a very good activity. The isobolar equivalent (IE) calculated from the ED90 of PCE incombination with artesunic acid showed that the interaction was antagonistic.Interpretation & conclusion: Although pawpaw alone was found to have a very good activity, its combinationwith artesunic acid is antagonistic. Combinations of artemisinins and pawpaw show little promise forcombination therapy development