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Biochim Biophys Acta Gen Subj ; 1865(3): 129813, 2021 03.
Article in English | MEDLINE | ID: mdl-33321150

ABSTRACT

BACKGROUND: Malaria is a parasitic disease that compromises the human host. Currently, control of the Plasmodium falciparum burden is centered on artemisinin-based combination therapies. However, decreased sensitivity to artemisinin and derivatives has been reported, therefore it is important to identify new therapeutic strategies. METHOD: We used human erythrocytes infected with P. falciparum and experimental cerebral malaria (ECM) animal model to assess the potential antimalarial effect of eugenol, a component of clove bud essential oil. RESULTS: Plasmodium falciparum cultures treated with increasing concentrations of eugenol reduced parasitemia in a dose-dependent manner, with IC50 of 532.42 ± 29.55 µM. This effect seems to be irreversible and maintained even in the presence of high parasitemia. The prominent effect of eugenol was detected in the evolution from schizont to ring forms, inducing important morphological changes, indicating a disruption in the development of the erythrocytic cycle. Aberrant structural modification was observed by electron microscopy, showing the separation of the two nuclear membrane leaflets as well as other subcellular membranes, such as from the digestive vacuole. Importantly, in vivo studies using ECM revealed a reduction in blood parasitemia and cerebral edema when mice were treated for 6 consecutive days upon infection. CONCLUSIONS: These data suggest a potential effect of eugenol against Plasmodium sp. with an impact on cerebral malaria. GENERAL SIGNIFICANCE: Our results provide a rational basis for the use of eugenol in therapeutic strategies to the treatment of malaria.


Subject(s)
Antimalarials/pharmacology , Brain Edema/drug therapy , Eugenol/pharmacology , Life Cycle Stages/drug effects , Malaria, Cerebral/drug therapy , Malaria, Falciparum/drug therapy , Plasmodium falciparum/drug effects , Animals , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/parasitology , Brain Edema/parasitology , Disease Models, Animal , Erythrocytes/drug effects , Erythrocytes/parasitology , Humans , Inhibitory Concentration 50 , Life Cycle Stages/physiology , Malaria, Cerebral/parasitology , Malaria, Falciparum/parasitology , Male , Mice , Mice, Inbred C57BL , Plasmodium berghei/drug effects , Plasmodium berghei/growth & development , Plasmodium berghei/parasitology , Plasmodium falciparum/growth & development , Plasmodium falciparum/pathogenicity
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