Inhibition of in-vitro growth of Plasmodium falciparum by Pseudocedrela kotschyi extract alone and in combination with Fagara zanthoxyloides extract.

Roots of Pseudocedrela kotschyi are commonly used as chewing sticks in West Africa. This study examined the effects of the plant extract on the in-vitro growth of Plasmodium falciparum. Ring-stage synchronised cultures of the malaria parasite were exposed to 30 and 60 microg/ml of P. kotschyi extract for 51 h. Aliquots were taken from the cultures every 3 h for preparation of Giemsa-stained thin films, which were evaluated by light microscopy for degree of parasitaemia and stage distribution of parasite development. The extracts did not show any inhibitory effects on the emergence of trophozoites in treated cultures. However, the results indicate that 80% of inhibition of the parasite transformation into schizont was obtained for both tested concentrations (30 and 60 microg/ml). Experiments with (3)H-hypoxanthine incorporation showed an IC(50) of 16 microg/ml for the Pseudocedrela extract. Pseudocedrela was combined with extract of Fagara zanthoxyloides in various concentrations to determine their interactive effects on the in-vitro cultures. Isobologram analysis of the results indicated a synergistic interaction between the two extracts at low concentrations, while interactions at higher concentrations showed antagonistic effects.

Effects of root extracts of Fagara zanthoxyloides on the in vitro growth and stage distribution of Plasmodium falciparum.

The development of resistance by Plasmodium falciparum to conventional drugs poses a threat to malaria control. There is therefore a need to find new, effective, and affordable remedies for malaria, including those derived from plants. This study demonstrates that crude, reverse-phase high-pressure liquid chromatography (RP-HPLC)-semipurified, and RP-HPLC-purified root extracts of Fagara zanthoxyloides inhibit the growth of P. falciparum in vitro, with 50% inhibitory concentrations (IC(50)s) of 4.90, 1.00, and 0.13 microg/ml, respectively. Roots of F. zanthoxyloides, known as chewing sticks, are widely used for tooth cleaning in West Africa. Microscopic examination of Giemsa-stained slides showed a virtual absence of schizonts in ring-stage synchronized cultures treated with crude extracts at concentrations of 30 to 60 microg/ml during 36 to 48 h of incubation. These observations suggest that the active constituent in the extract may be cytotoxic for P. falciparum trophozoites, thereby inhibiting their development to the schizont stage. A pure bioreactive fraction was subsequently obtained from the chromatographic separations. When this fraction was mixed with pure fagaronine, the mixture coeluted as a single peak on the analytical RP-HPLC column, suggesting that fagaronine may be the active antimalarial constituent of Fagara root extracts. Additional experiments showed that fagaronine also inhibited P. falciparum growth, with an IC(50) of 0.018 microg/ml. The results of this study suggest that the antimalarial activity of fagaronine deserves further investigation.