title: Antagonistic antimalarial properties of pawpaw leaf aqueous extract in combination with artesunic acid in Plasmodium berghei-infected mice.
abstract: OBJECTIVE
  Artemisinins, the main stay in the treatment of malaria are used in combinations with other antimalarials to forestall resistance, as artemisinin-combination therapies (ACTs). However, ACTs are expensive and some of the non-artemisinin components are not well-tolerated by patients. There are several folkloric and scientific proofs of the efficacy of herbal remedies for malaria. Mature leaves of Carica papaya is widely used to treat malaria in several African countries. An ACT involving a medicinal herb extract or 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 h and the extract (PCE) was stored in the refrigerator for seven days. Fresh extracts were made as needed. The antiplasmodial activity of PCE and/or artesunic acid were determined by using the Peter's 4-day suppressive test in Plasmodium berghei-infected mice. The ED50 and ED90 were calculated from the dose-response relationships.
  
  
  RESULTS
  The combination of 50 mg/kg of PCE and 15 mg/kg of artesunic acid produced a significant reduction of parasitemia (81.25%), compared to 50 mg/kg PCE alone (37.7%). The mean survival time of the combinations of PCE and 15 mg/kg of artesunic acid, and PCE alone followed a dose-dependent manner. The ED50 of PCE showed that it has a very good activity. The isobolar equivalent (IE) calculated from the ED90 of PCE in combination with artesunic acid showed that the interaction was antagonistic.
  
  
  CONCLUSIONS
  Although pawpaw alone was found to have a very good activity, its combination with artesunic acid is antagonistic. Combinations of artemisinins and pawpaw show little promise for combination therapy development.
authors.affiliation: Department of Pharmaceutics, University of Nigeria, Nsukka, Nigeria. onakuonyeka@yahoo.com
authors.forename: L O
authors.initials: LO
authors.lastname: Onaku
authors.forename: A A
authors.initials: AA
authors.lastname: Attama
authors.forename: V C
authors.initials: VC
authors.lastname: Okore
authors.forename: A Y
authors.initials: AY
authors.lastname: Tijani
authors.forename: A A
authors.initials: AA
authors.lastname: Ngene
authors.forename: C O
authors.initials: CO
authors.lastname: Esimone
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use*; D031042:Asimina; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D008288:Malaria / Q000188:drug therapy* / Q000517:prevention & control; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves; D010962:Plasmodium berghei / Q000187:drug effects*; D013386:Succinates / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D010936:Plant Extracts; D013386:Succinates; C111789:artesunic acid