title: In vitro and in vivo combination of cepharanthine with anti-malarial drugs.
abstract: BACKGROUND
  Stephania rotunda is used by traditional health practitioners in Southeast Asia to treat a wide range of diseases and particularly symptoms related to malaria. Cepharanthine (CEP) is an alkaloid isolated from this plant with potential innovative antiplasmodial activity. The analysis of interactions between antiplasmodial drugs is necessary to develop new drugs combinations to prevent de novo emergence of resistance. The objective of this study was to evaluate the anti-malarial activity of CEP in combination with usual anti-malarial compounds, both in vitro and in vivo.
  
  
  METHODS
  A fixed ratio method using the isotopic micro test was performed on the chloroquine-resistant plasmodial strain W2 to build isobolograms from eight CEP-based combinations with standard anti-malarial drugs. The efficacy of two combinations was then evaluated in the BALB/c mouse infected with Plasmodium berghei ANKA strain.
  
  
  RESULTS
  In vitro, efficiency gains were observed when CEP was combined with chloroquine (CQ), lumefantrine (LUM), atovaquone (ATO), piperaquine (PPQ) and particularly monodesethylamodiaquine (MdAQ), whereas an antagonistic interaction was observed with dihydroartemisinin (DHA) and mefloquine (MQ). In vivo, the combination of CEP with CQ or amodiaquine (AQ) improved significantly the survival of mice and extended the delay for parasitic recrudescence.
  
  
  CONCLUSIONS
  All these observations suggest that CEP could be an interesting lead compound in the development of a combination therapy against malaria.
authors.forename: Camille
authors.initials: C
authors.lastname: Desgrouas
authors.forename: Jérôme
authors.initials: J
authors.lastname: Dormoi
authors.forename: Charles
authors.initials: C
authors.lastname: Chapus
authors.forename: Evelyne
authors.initials: E
authors.lastname: Ollivier
authors.forename: Daniel
authors.initials: D
authors.lastname: Parzy
authors.affiliation: UMR - MD3, Faculté de pharmacie, Aix-Marseille-Université, Marseille, France. nicolas.taudon@gmail.com.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Taudon
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D044182:Benzylisoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D021261:Parasitic Sensitivity Tests; D010962:Plasmodium berghei / Q000187:drug effects*; D016019:Survival Analysis; D016896:Treatment Outcome; D052117:Benzodioxoles
chemical_list: D000962:Antimalarials; D044182:Benzylisoquinolines; C006947:cepharanthine; D052117:Benzodioxoles