Evaluation of the antimalarial activity of Glinus oppositifolius (L. ) Aug. D. C. , Nauclea latifolia SM. Mitragyna inermis (Willd. ) O. Kuntze: three plants used in traditional medicine in Mali.

Summary Malaria is a major public health problem in sub-Saharan Africa and in particular in Mali. The decreasing efficacy of classical antimalarial drugs in relation to the rapid progression of chloroquine-resistant strains of Plasmodium falciparum justifies the search for new antimalarial drugs. Difficulty in accessing health care and modern medicines, as well as certain socio-cultural behaviors, mean that a large part of the population resorts to traditional therapists for febrile illnesses. After three series of surveys conducted among traditional therapists, we selected three plants: Mitragyna inermis (Willd. ) O. Kuntze, Glinus oppositifolius (L) Aug. D. C. And Nauclea latifolia Sm. Structural determination of the isolated molecules was done by mass spectrometry and nuclear magnetic resonance methods. From the leaves of M. Inermis, we isolated for the first time ursolic acid and two alkaloids already described among the total alkaloids: speciophyllin and isorhyncophyllin. The determination of alkaloids in leaves and aqueous extracts of traditional preparations of this plant allowed us to retain the 60% hydroethanol extract for further studies. The aerial parts of G. Oppositifolius provided two new compounds: 16-O (β-D-arabinopyranosyl)-3-oxo-12, 16β ,21β22-tetrahydroxy-hopane named Glinoside A and 16-O (β-D-arabinopyranosyl)-3-oxo-12, 16β, 22-trihydroxy-hopane named Glinoside B. Regarding N. Latifolia, the search for saponosides was negative and we did not pursue the fractionation of alkaloids due to cytotoxicity and genotoxicity of total alkaloids. The antiplasmodial activity of the crude extracts, fractions and pure compounds was investigated in vitro on two strains of chloroquine-sensitive and chloroquine-resistant P. Falciparum by measuring the inhibition of proliferation. The reading was done both by light microscopy and flow cytometry. None of the aqueous extracts of the three plants made in the laboratory were active at the concentration of 500 µg/ml. The IC50 of the hydromethanolic extracts is between 100 and 500 µg/ml. The saponosides of G. Oppositifolius have an IC50 of 40 µg/ml but we abandoned pharmacological studies because of the rarity of the plant. The total alkaloids of N. Latifolia are active at the concentration of 5µg/ml. They are also cytotoxic at this same concentration. The aqueous extracts of the traditional preparations of M. Inermis are active at the concentration of 250 µg/ml. Ursolic acid has a higher antiplasmodial activity (IC50=15µg/ml) than the hydromethanolic extract of M. Inermis leaves from which it is derived. The best antiplasmodial activity was obtained with total alkaloids with IC50s of 4-6 µg/ml. The total alkaloids of M. Inermis and the 60% hydroethanolic extract were free of toxicity at the concentrations tested. Their antimalarial activity was also tested in vivo on mice experimentally infested with P. Berghei. The alkaloids are not very active at a dose of 250 mg/kg with a decrease in parasitemia of 20%. On the other hand, the hydroethanolic extract causes an 80% reduction in parasitemia at a dose of 1 g/kg.