title: Traditional herbal antimalarial therapy in Kilifi district, Kenya.
abstract: OBJECTIVE
  To identify plant species used by the traditional health practitioners (THPs) in treatment of malaria, carry out cytotoxicity and efficacy evaluation of the identified plants and to evaluate combination effects.
  
  
  METHODS
  Thirteen plants were selected through interviews with traditional healers. In vitro antiplasmodial testing was done by measuring ability of the test sample to inhibit the incorporation of radio-labelled hypoxanthine into the malaria parasite. The extracts were tested singly and then in combination using the standard fixed ratio analysis to evaluate synergism. In vivo bioassay was done in mice using Peter's 4-days suppressive test and cytotoxicity evaluated in vitro using Vero E6 cells.
  
  
  RESULTS
  Of the plants tested in vitro, 25% were highly active (IC(50)<10 μg/ml), 46% moderately active (IC(50) 10-50 μg/ml), 16% had weak activity of 50-100 μg/ml while 13% were not active IC(50) >100 μg/ml. Methanolic extracts of Azadirachta indica, Premna chrysoclada and Uvaria acuminata were the most active (IC(50)<10μg/ml) against both the chloroquine (CQ) sensitive (D6) and the CQ resistant (W2) Plasmodium falciparum clones. When tested in vivo in a mouse model, Azadirachta indica, Rhus natalensis and Grewia plagiophylla depicted the highest percent parasite clearance and chemo suppression of 89%, 82% and 78%, respectively. Evaluating effect of combining some of these extracts with one another against a multi-drug resistant Plasmodium falciparum (W2) clone revealed synergism among some combinations. The highest synergy was between Uvaria acuminata and Premna chrysoclada. The interaction between Grewia plagiophylla and Combretum illairii was largely antagonistic. Impressive cytotoxicity results were obtained with most of the plants tested revealing high selectivity indices an indication of enabling achievement of therapeutic doses at safe concentrations. Uvaria acuminata was, however, toxic to the cultured cells. Mild cytotoxicity was also observed in Hoslundia opposita and Lannea schweinfurthii (CC(50) 37 and 76 μg/ml, respectively).
  
  
  CONCLUSIONS
  This study identified plants with low IC(50) values, high percent chemo suppression and low cytotoxicity thus potential sources for novel antiplasmodial agents. The findings remotely justify use of combined medicinal plants in traditional medicine practices as synergy among some plant species was demonstrated.
authors.affiliation: Kenya Medical Research Institute (KEMRI), P.O. Box 54840 00200, Nairobi, Kenya. jgathirwa@kemri.org
authors.forename: J W
authors.initials: JW
authors.lastname: Gathirwa
authors.forename: G M
authors.initials: GM
authors.lastname: Rukunga
authors.forename: P G
authors.initials: PG
authors.lastname: Mwitari
authors.forename: N M
authors.initials: NM
authors.lastname: Mwikwabe
authors.forename: C W
authors.initials: CW
authors.lastname: Kimani
authors.forename: C N
authors.initials: CN
authors.lastname: Muthaura
authors.forename: D M
authors.initials: DM
authors.lastname: Kiboi
authors.forename: R M
authors.initials: RM
authors.lastname: Nyangacha
authors.forename: S A
authors.initials: SA
authors.lastname: Omar
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D002522:Chlorocebus aethiops; D018432:Drug Resistance, Multiple / Q000187:drug effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D007630:Kenya; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D016488:Medicine, African Traditional; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008517:Phytotherapy; D010936:Plant Extracts / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000009:adverse effects; D010963:Plasmodium falciparum / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D000962:Antimalarials; D010936:Plant Extracts