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In Mali, where malaria is endemic, plants are extensively used for treating periodic fevers and malaria. According to the advice of traditional medicine, plants are often mixed during the preparation of febrifugal decoctions. In previous studies, we demonstrated the potent in vitro antimalarial activity of extracts isolated from four plants commonly used in traditional remedies: Mitragyna inermis (Willd.) O. Kuntze, Rubiaceae, Nauclea latifolia (Sm.), Rubiaceae, Guiera senegalensis (Gmel.), Combretaceae, and Feretia apodanthera (Del.), Rubiaceae. In the present work, we evaluate the potent in vitro synergistic antimalarial interaction between these extracts, using standard isobologram analysis. Then, we evaluate their cytotoxicity on human monocytes and their mutagenic activity on an in vitro system of two beta-carboline alkaloids isolated from Guiera senegalensis (harman and tetrahydroharman). Three combinations demonstrate a strong, synergistic, inhibitory effect on in vitro plasmodial development and are devoid of cytotoxicity towards human cells. These results justify their use in association in traditional medicine. Moreover, tetrahydroharman, isolated from G. senegalensis, presents interesting antimalarial activity, no cytotoxicity and is not genotoxic in the Salmonella Ames test with and without metabolic activation.

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The in vitro antileishmanial activity of three saponins isolated from ivy, alpha-hederin, beta-hederin and hederacolchiside A1, was investigated on Leishmania infantum. The assessment of possible targets (membrane integrity, membrane potential, DNA synthesis and protein content) was performed in both Leishmania promastigotes and human monocytes (THP1 cells). Results observed in Leishmania showed that the saponins exhibited a strong antiproliferative activity on all stages of development of the parasite by altering membrane integrity and potential: hederacolchiside A1 appeared to be the most active compound against both promastigotes and amastigotes. Results observed in THP1 cells demonstrated that the saponins exerted also a potent antiproliferative activity against human monocytes, by producing a significant DNA synthesis inhibition. The ratio between antileishmanial activity on amastigotes and toxicity to human cells suggested that the saponins could be considered as possible antileishmanial drugs.

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Mitragyna inermis (De Willd.) O. Kuntze Rubiaceae, Nauclea latifolia (Sm.) Rubiaceae, Glinus oppositofolius (Linn) Molluginaceae and Trichilia roka (Forsk.) Chiv. Meliaceae were investigated for their in vitro antimalarial activity. Leaves, roots and stem barks were submitted to aqueous, hydromethano and chloroform extractions and antimalarial activity was evaluated by microscopic and flow cytometric analysis. The results present evidence that the alkaloids contained in chloroform extracts and ursolic acid, purified from the hydromethanol extract of M. inermis induced a significant decrease of parasite proliferation. However, aqueous extracts, traditionally used for medication did not show high antimalarial activity. Statistical comparison between microscopic and cytometric analysis demonstrated the validity of this new technique for the screening of active antimalarial compounds isolated from plants. Copyright ­© 2000 John Wiley & Sons, Ltd.