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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

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

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Raceline G Kamkumo, Alvine M Ngoutane, Lauve RY Tchokouaha, Patrick VT Fokou, Eugénie AK Madiesse, Jennifer Legac, Jean JB Kezetas, Bruno N Lenta, Fabrice F Boyom, Theophile Dimo, Wilfred F Mbacham, Jiri Gut, Philip J Rosenthal
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-382) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

FFB and RGK participated in plant selection and collection, and analyzed botanical/ethnomedicinal data in collaboration with the ethnobotanist. RGK, AMN, LRTY, PVTF, EAKM carried out the in vitro (on isolates) and in vivo anti-plasmodial assays that were conceived, designed and coordinated by FFB and WFM. They also contributed to data analysis and manuscript drafting. JJB and BNL carried out the phytochemical study of the plant sample and structure elucidation. TD designed and coordinated the toxicity studies and contributed to the manuscript drafting. JL and JG carried out the in vitro assays against Plasmodium falciparum W2 and falcipain 2 and also contributed to manuscript drafting. These studies were conceived and coordinated by PJR who also critically improved the quality of the manuscript. All the authors read and approved the final version of manuscript.

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.
Zusatzmaterial
Additional file 1: Inhibition of P. falciparum isolates by Sorindeia juglandifolia fractions and purified compounds. (DOCX 17 KB)
12936_2012_2532_MOESM1_ESM.docx
Authors’ original file for figure 1
12936_2012_2532_MOESM2_ESM.pdf
Authors’ original file for figure 2
12936_2012_2532_MOESM3_ESM.pdf
Literatur
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