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Open Access Research

Compounds from Sorindeia juglandifolia (Anacardiaceae) exhibit potent anti-plasmodial activities in vitro and in vivo

Raceline G Kamkumo12, Alvine M Ngoutane2, Lauve RY Tchokouaha2, Patrick VT Fokou2, Eugénie AK Madiesse23, Jennifer Legac5, Jean JB Kezetas4, Bruno N Lenta4, Fabrice F Boyom2*, Theophile Dimo1, Wilfred F Mbacham3, Jiri Gut5 and Philip J Rosenthal5

Author Affiliations

1 Laboratory of Animal Physiology, Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, PO Box 812, Yaoundé, Cameroon

2 Laboratory for Phytobiochemistry and Medicinal Plants Studies, Department of Biochemistry, Faculty of Science, University of Yaoundé 1, PO Box 812, Yaoundé, Cameroon

3 Laboratory for Public Health Research Biotechnologies, Biotechnology Centre, University of Yaoundé 1, PO Box 8094, Yaoundé, Cameroon

4 Department of Chemistry, Faculty of Science, University of Bamenda, Bamenda, Cameroon

5 Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, 94943, USA

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Malaria Journal 2012, 11:382  doi:10.1186/1475-2875-11-382

Published: 21 November 2012

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.

Keywords:
Malaria; Drug discovery; Sorindeia juglandifolia; Plasmodium falciparum; Plasmodium berghei