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Eugenol disrupts Plasmodium falciparum intracellular development during the erythrocytic cycle and protects against cerebral malaria

2020; Elsevier BV; Volume: 1865; Issue: 3 Linguagem: Inglês

10.1016/j.bbagen.2020.129813

1872-8006

Kesley A.O. Pontes, Leandro S. Silva, Edgleyson C. Santos, Alessandro S. Pinheiro, Douglas E. Teixeira, Diogo B. Peruchetti, Rodrigo P. Silva‐Aguiar, Camila Wendt, Kildare Miranda, Andrelina Noronha Coelho‐de‐Souza, José Henrique Leal‐Cardoso, Celso Caruso‐Neves, Ana Acácia S. Pinheiro,

Mosquito-borne diseases and control

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. 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. 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. These data suggest a potential effect of eugenol against Plasmodium sp. with an impact on cerebral malaria. Our results provide a rational basis for the use of eugenol in therapeutic strategies to the treatment of malaria.