Potentials of Terpenoids as Inhibitors of Multiple Plasmodium falciparum Protein Drug Targets.

PURPOSE: The resistance of parasite to readily affordable antimalarial drugs, the high cost of currently potent drugs, and the resistance of vector mosquitoes to insecticides threaten the possibility of malaria eradication in malaria endemic areas. Due to the fact that quinine and artemisinin were isolated from plants sources, researchers have been encouraged to search for new antimalarials from medicinal plants. This is especially the case in Africa where a large percentage of the population depends on medicinal plant to treat malaria and other ailments. METHOD: In this study, we evaluated previously characterized Plasmodium-cidal compounds obtained from the African flora to identify their likely biochemical targets, for an insight into their possible antimalarial chemotherapy. Molecular docking study was first conducted, after which remarkable compounds were submitted for molecular dynamic (MD) simulations studies. RESULTS: From a total of 38 Plasmodium-cidal compounds docked with confirmed Plasmodium falciparum protein drug targets [plasmepsin II (PMII), histo-aspartic protein (HAP) and falcipain-2 (FP)], two pentacyclic triterpene, cucurbitacin B and 3 beta-O-acetyl oleanolic acid showed high binding affinity relative to artesunate. This implies their capacity to inhibit the three selected P. falciparum target proteins, and consequently, antimalarial potential. From the MD simulations studies and binding free energy outcomes, results confirmed that the two compounds are stable in complex with the selected antimalarial targets; they also showed excellent binding affinities during the 100 ns simulation. CONCLUSION: These results showed that cucurbitacin B and 3 beta-O-acetyl oleanolic acid are potent antimalarials and should be considered for further studies.

Ethanolic extract of Clerodendrum violaceum Gürke leaves enhances kidney function in mouse model of malaria.

Evaluation of the effects of daily oral administration of ethanolic extract of C. violaceum leaves (13 mg/kg body weight) for 5 days on some kidney function indices of uninfected and Plasmodium berghei-infected mice was done on days 3, 8 and 14 post-infection. The indices studied include serum urea and creatinine concentrations with the specific activities of alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase in the kidney. Treatment of P. berghei-infected mice with ethanolic extract of C. violaceum leaves (13 mg/kg body weight) for 5 days was able to ameliorate significantly the alterations in the various parameters observed in infected untreated mice, comparing favourably with chloroquine treatment in most cases. Administration of extract to uninfected mice had no significant effect on both serum and kidney parameters compared to the uninfected control. The results suggest that the ethanolic extract of C. violaceum leaves does not adversely affect kidney function at the dose used in traditional medicine for the treatment of malaria but rather enhances it.

Analgesic and anti-inflammatory properties of Nelsonia canescens leaf extract.

An ethanolic extract of the dried leaves of Nelsonia canescens was investigated for anti-inflammatory and analgesic activities in rat. In the test for anti-inflammatory activity, the extract at the doses of 50-200 mg/kg significantly (P<0.05) inhibited carrageenan-induced paw oedema and cotton pellet granuloma. Likewise, at the same doses the extract exhibited analgesic activity in both the hot plate latency assay (hot plate maintained at 55 degrees C) and on the early and late phases of formalin-induced paw licking in rats. The result of the present study confirm that Nelsonia canescens has analgesic and anti-inflammatory activities. These findings also justify the traditional use of the plant for treating pain.