title: Protective activity of biflavanones from Garcinia kola against Plasmodium infection.
abstract: BACKGROUND
  Garcinia kola is a medicinal plant traditionally used for malaria therapy in Central Africa.
  
  
  OBJECTIVE
  To evaluate the antimalarial potencies in vitro and in vivo of pure biflavanones from G. kola.
  
  
  METHODS
  The pure biflavanones were obtained by bioassay-guided fractionation of a 70% ethanol extract of G. kola seeds and their chemical structures were elucidated by comparison of their NMR ((1)H and (13)C) and mass spectral data with those provided in the literature. Plasmodium falciparum (FCR-3, cycloguanil-resistant strain from Gambia) was used for in vitro assessments of antimalarial activities. Growth inhibition, intraerythrocytic development and parasite morphology were evaluated in culture by the microscopic observation of Giemsa-stained thin blood films. The cytotoxicity of the antimalarial compounds was evaluated against KB 3-1 (human epidermoid carcinoma) cells by MTT assay. In vivo antimalarial activities were determined in mice infected with Plasmodium berghei (ANKA strain) following a four-day suppressive test.
  
  
  RESULTS
  The bioassay-guided fractionation of an extract of G. kola resulted in the isolation of three biflavanones (GB-1a, GB-1, and GB-2) as its active principles. These three biflavanones displayed not only potent inhibitory activity in vitro against P. falciparum proliferation but also antimalarial potency through oral administration in mice infected with P. berghei without signs of acute toxicity. GB-1 was found to exhibit the strongest in vitro antimalarial potency on P. falciparum with an IC50 of 0.16μM, whereas it exhibited a very low in vitro cytotoxicity on KB 3-1 cells with an IC50 of greater than 150μM. During an in vivo antimalarial assay in mice infected with P. berghei, GB-1 was found to exhibit biological potency with an approximate ED50 of 100mg/kg following oral administration. GB-1 was also shown to increase the average life span of the infected mice significantly compared to that of control mice (p<0.01 Student's t-test).
  
  
  CONCLUSIONS
  The antimalarial outcome of GB-1a, GB-1, and GB-2 may be related to the traditional utilization of this crude drug against malaria judging from their significant content in G. kola nuts. GB-1 showed the most potent antimalarial activity with a high selectivity index and, therefore could be exploited to identify the molecular target, which subsequently could be helpful to design novel therapeutics against malaria. GB-1 may be considered a promising antimalarial candidate for trial in vivo using higher animals infected with P. falciparum.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan. Electronic address: benetode@hotmail.com.
authors.forename: Benetode
authors.initials: B
authors.lastname: Konziase
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D045744:Cell Line, Tumor; D044950:Flavanones / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D029763:Garcinia kola / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D016778:Malaria, Falciparum / Q000188:drug therapy; D008297:Male; D016488:Medicine, African Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D012639:Seeds
chemical_list: D000962:Antimalarials; D044950:Flavanones; D010936:Plant Extracts
keywords: Biflavanone; Bioassay-guided fractionation; Garcinia kola; Malaria; Plasmodium; Protective activity