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Journal of Ethnopharmacology 2010-Aug

Antimalarial activity and toxicity evaluation of a quantified Nauclea pobeguinii extract.

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Kahunu Mesia
Richard K Cimanga
Liene Dhooghe
Paul Cos
Sandra Apers
Jozef Totté
Gaston L Tona
Luc Pieters
Arnold J Vlietinck
Louis Maes

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Astratto

OBJECTIVE

To evaluate the in vitro and in vivo antiplasmodial activity and toxicity of the aqueous and 80% EtOH extract of the stem bark of Nauclea pobeguinii (Pob. Ex. Pell.) Petit (Rubiaceae), a plant used in traditional medicine in DR Congo against malaria.

METHODS

The aqueous and 80% EtOH extract from N. pobeguinii stem bark, and its constituents (5S)-5-carboxystrictosidine, 19-O-methylangustoline, 3-O-beta-fucosylquinovic acid, 3-ketoquinovic acid and strictosamide, were evaluated for their in vitro activity against Plasmodium falciparum (chloroquine-sensitive Ghana-strain). The 80% EtOH extract, containing 5.6% strictosamide, was evaluated in vivo in the 4-day P. berghei mouse model, and in the P. yoelii N67 model.

RESULTS

All compounds were inactive or only moderately active in vitro. The aqueous and 80% EtOH extract displayed moderate in vitro activity with IC(50) values of 44 and 32 microg/mL, respectively, without apparent cytotoxicity on MRC-5 cells (CC50>64 microg/mL). Daily oral dosing of the 80% EtOH extract, at 300 mg/kg, resulted in 86% reduction of parasitaemia in the 4-day P. berghei mouse model, and 75% reduction in the P. yoelii N67 model. Prolonging oral dosing to 2 x 5 days, with an interval of 2 days, and oral administration of the 80% EtOH extract at 300 mg/kg induced 92% reduction of parasitaemia, and a mean survival time of 17 days. Strictosamide, the putative active constituent, may be metabolically activated in the gastrointestinal tract after oral administration. Levels of creatinin, urea, ALAT and ASAT remained unchanged after treatment. No acute toxicity was observed in mice after a single 2g/kg oral dose, nor after 4 weekly doses. No significant macroscopic or microscopic lesions were observed in heart, lung, spleen, kidney, liver, large intestine and brain.

CONCLUSIONS

These results can partly support and justify the use of N. pobeguinii in traditional medicine in the DR Congo for the treatment of uncomplicated malaria.

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