title: Compounds from Sorindeia juglandifolia (Anacardiaceae) exhibit potent anti-plasmodial activities in vitro and in vivo.
abstract: BACKGROUND
  Discovering new lead compounds against malaria parasites is a crucial step to ensuring a sustainable global pipeline for effective anti-malarial drugs. As far as we know, no previous phytochemical or pharmacological investigations have been carried out on Sorindeia juglandifolia. This paper describes the results of an anti-malarial activity-driven investigation of the fruits of this Cameroonian plant.
  
  
  METHODS
  Air-dried fruits were extracted by maceration using methanol. The extract was fractionated by flash chromatography followed by column chromatography over silica gel, eluting with gradients of hexane-ethyl acetate mixtures. Resulting fractions and compounds were tested in vitro against the Plasmodium falciparum chloroquine-resistant strain W2, against field isolates of P. falciparum, and against the P. falciparum recombinant cysteine protease falcipain-2. Promising fractions were assessed for acute toxicity after oral administration in mice. One of the promising isolated compounds was assessed in vivo against the rodent malaria parasite Plasmodium berghei.
  
  
  RESULTS
  The main end-products of the activity-guided fractionation were 2,3,6-trihydroxy benzoic acid (1) and 2,3,6-trihydroxy methyl benzoate (2). Overall, nine fractions tested against P. falciparum W2 and falcipain-2 were active, with IC50 values of 2.3-11.6 μg/ml for W2, and 1.1-21.9 μg/ml for falcipain-2. Purified compounds (1) and (2) also showed inhibitory effects against P. falciparum W2 (IC50s 16.5 μM and 13.0 μM) and falcipain-2 (IC50s 35.4 and 6.1 μM). In studies of P. falciparum isolates from Cameroon, the plant fractions demonstrated IC50 values of 0.14-19.4 μg/ml and compounds (1) and (2) values of 6.3 and 36.1 μM. In vivo assessment of compound (1) showed activity against P. berghei strain B, with mean parasitaemia suppressive dose and curative dose of 44.9 mg/kg and 42.2 mg/kg, respectively. Active fractions were found to be safe in mice after oral administration of 7 g/kg body weight.
  
  
  CONCLUSIONS
  Fractions of Sorindeia juglandifolia and two compounds isolated from these fractions were active against cultured malaria parasites, the P. falciparum protease falcipain-2, and in a rodent malaria model. These results suggest that further investigation of the anti-malarial activities of natural products from S. juglandifolia will be appropriate.
authors.affiliation: Laboratory for Phytobiochemistry and Medicinal Plants Studies, Department of Biochemistry, Faculty of Science, University of Yaoundé 1, PO Box 812, Yaoundé, Cameroon.
authors.forename: Raceline G
authors.initials: RG
authors.lastname: Kamkumo
authors.forename: Alvine M
authors.initials: AM
authors.lastname: Ngoutane
authors.forename: Lauve R Y
authors.initials: LR
authors.lastname: Tchokouaha
authors.forename: Patrick V T
authors.initials: PV
authors.lastname: Fokou
authors.forename: Eugénie A K
authors.initials: EA
authors.lastname: Madiesse
authors.forename: Jennifer
authors.initials: J
authors.lastname: Legac
authors.forename: Jean J B
authors.initials: JJ
authors.lastname: Kezetas
authors.forename: Bruno N
authors.initials: BN
authors.lastname: Lenta
authors.forename: Fabrice F
authors.initials: FF
authors.lastname: Boyom
authors.forename: Theophile
authors.initials: T
authors.lastname: Dimo
authors.forename: Wilfred F
authors.initials: WF
authors.lastname: Mbacham
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D002845:Chromatography; D004195:Disease Models, Animal; D005260:Female; D008288:Malaria / Q000188:drug therapy; D008297:Male; D051379:Mice; D021261:Parasitic Sensitivity Tests; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D029631:Sapindaceae / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D010936:Plant Extracts