title: Potential of a Khaya ivorensis -Alstonia boonei extract combination as antimalarial prophylactic remedy.
abstract: BACKGROUND
  The decoction of the combined stem barks of Khaya ivorensis A. Chev. (Meliaceae) and Alstonia boonei De Wild (Apocynaceae) has a history of use in traditional medicine of central Cameroon for malaria treatment but also for the prevention of the disease.
  
  
  OBJECTIVE
  The purpose of this investigation was to determine the antiplasmodial activity of Khaya ivorensis (K) and Alstonia boonei (A) preparations in the murine malaria model Plasmodium berghei/Anopheles stephensi, to estimate their prophylactic potential and to assess acute and sub-acute toxicity of the formulations prepared according to the traditional recipes.
  
  
  METHODS
  Aqueous extracts from the stem-bark of the two plants were prepared and tested separately and in combination. BALB/c mice were treated for 9 days and challenged on day 3 by exposure to mosquitoes infected with Plasmodium berghei. Treatment doses ranged between 200 and 400mg/kg/day, corresponding approximately to the dosage applied by traditional healers to cure malaria patients or prevent the disease. Parasitemia reduction in treated animals was calculated from Giemsa smear counts, of two replicate experiments. To estimate acute toxicity in terms of median lethal dose (LD50), geometrically increasing doses were administered to mice. Sub-acute toxicity of the herbal combination (KA) was investigated by administering the same doses as in the antiplasmodial activity test for a period of 14 days, followed by 14 days of recovery observation. Locomotor activity (Open Field Test), body weight, liver and kidney morphology were monitored.
  
  
  RESULTS
  The combination KA was found to exhibit antiplasmodial activity in the murine malaria model. In mice treated with the combination remedy at a dosage of 200mg/kg/day, parasitemia values of 6.2% ± 1.7 and 6.5% ± 0.8 were recorded, compared to 10.8% ± 1.3 and 12.0% ± 4.0 in controls (p<0.01). Doubling the dosage of the extracts did not significantly increase parasite suppression. When extracts of K and A were administered separately at a dosage of 400mg/kg, a reduction in parasitemia was still obtained, but it did not reach statistical significance. Toxicity studies yielded comforting results: the LD50 was estimated to be greater than 2779.5mg/kg. Moreover, mice exposed to the fourteen-day repeated-dose toxicity test (sub-acute toxicity test) did not display weight loss, liver or kidney morphological modifications, significant alterations in locomotor activity or any other sign of illness.
  
  
  CONCLUSIONS
  The antiplasmodial activity and the wide dose interval between the therapeutic dosage and the toxic dosage exhibited by the KA herbal combination in the murine malaria model argue in favor of its use as an antimalarial prophylactic remedy. It remains to be demonstrated by human clinical trials whether the combination remedy, when taken by inhabitants during malaria transmission season, can reduce parasite density and lead to a reduction of malaria episodes in the community.
authors: University of Camerino, School of Pharmacy, Piazza dei Costanti, 62032 Camerino (MC), Italy. roselyne.tepongning@unicam.it
authors: Roselyne Nzangue
authors: RN
authors: Tepongning
authors: Leonardo
authors: L
authors: Lucantoni
authors: Cinzia Carla
authors: CC
authors: Nasuti
authors: Geme Urge
authors: GU
authors: Dori
authors: Serge Rakiswende
authors: SR
authors: Yerbanga
authors: Giulio
authors: G
authors: Lupidi
authors: Carlotta
authors: C
authors: Marini
authors: Giacomo
authors: G
authors: Rossi
authors: Fulvio
authors: F
authors: Esposito
authors: Annette
authors: A
authors: Habluetzel
mesh_terms: D031051:Alstonia / Q000737:chemistry; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D007928:Lethal Dose 50; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008519:Medicine, Traditional; D029582:Meliaceae / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010270:Parasite Egg Count; D024301:Plant Bark; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D010946:Plants, Medicinal; D010962:Plasmodium berghei / Q000187:drug effects* / Q000472:pathogenicity; D018675:Toxicity Tests
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D010936:Plant Extracts