Abstract
BackgroundDrug resistance poses a challenge to malaria control measures. This calls for discovery & development of new chemotherapeutic agents. This study therefore was initiated to investigate the antimalarial activity of Olea europaea against Plasmodium berghei infected mice and to further ascertain in which fraction (s) the constituents responsible for anti-malarial activity are concentrated.MethodsThe leaves of Olea europaea were extracted by maceration using 80% methanol and the crude extract was then successively fractionated with solvents of differing polarity (chloroform, n-butanol and water). The anti-malarial activity of various doses of the extract and fractions (200, 400 and 600 mg/kg) was evaluated using chemo-suppressive, curative, and repository tests. Parameters, including parasitemia, rectal temperature, body weight, and packed cell volume were determined to establish the activity.ResultsThe acute oral toxicity test result revealed that the LD50 values of the extract and fractions were greater than 2000 mg/kg in mice. The crude extract significantly reduced parasitemia (p < 0.001) and prolonged survival time (p < 0.001), in a dose-dependent manner, in all tests, as compared to the negative control group. Higher parasitemia suppression (58%) was achieved with the larger dose (600 mg/kg) in the 4-day suppressive test, suggesting that the crude extract has largely a chemo-suppressive activity.Parasitemia was significantly reduced (p < 0.001) by all fractions in all doses used when compared to the negative controls, with the rank order of n-butanol (51%) > chloroform>aqueous (21%) fractions. Larger (600 mg/kg) and middle (400 mg/kg) doses of the crude extract as well as the fractions ameliorated all the other parameters in a consistent manner, with the crude being more active than the fractions. Preliminary phytochemical analysis revealed the presence of secondary metabolites that were differentially distributed in the fractions.ConclusionThe findings collectively indicate that the plant is endowed with antimalarial activity, the activity being more in the crude extract than the fractions, owing to the presence of secondary metabolites that act independently or in synergy. The varying degree of antimalarial activity in the fractions suggests that non-polar and medium polar principles could be responsible for the observed activity.
Highlights
Drug resistance poses a challenge to malaria control measures
Effect of 80% methanol extract in the 4-day suppressive test The results of the 4-day suppressive test indicated that the 80ME reduced (p < 0.001 in all cases) parasitemia in a dose-dependent manner compared to negative control, with percentage suppression of about 50, 55, 58 for 200 mg/kg, 400 mg/kg and 600 mg/kg doses, respectively (Table 1)
packed cell volume (PCV) determination revealed that the 80ME exhibited a statistically significant effect (p < 0.001) in the circumvention of PCV decline at all doses compared to the negative control even if the effect was still lower than the standard drug (p < 0.001 in all cases) (Table 2)
Summary
Drug resistance poses a challenge to malaria control measures. This calls for discovery & development of new chemotherapeutic agents. No single antimalarial drug is effective against all liver and intra-erythrocytic forms of the parasite, which could co-exist in the same patient. Efforts to develop an effective blood stage vaccine have not met with much success primarily because of antigenic diversity and a poor understanding of protective host immune responses [5, 6]. The genomic plasticity of the mosquito and the plasmodium parasite has added another dimension for the problem through increasing resistance to drugs, demanding an investment in research and development of newer agents for malaria control [6]. Traditional medicinal plants could be considered as an alternative source of new drugs, as some antimalarial drugs (quinine, artemisinin) in use today were of plant origin [7]
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