Dobinin K Displays Antiplasmodial Activity through Disruption of Plasmodium falciparum Mitochondria and Generation of Reactive Oxygen Species

Dobinin K is a novel eudesmane sesquiterpenoids compound isolated from the root of and displays potential antiplasmodial activity in vivo. Here, we evaluate the antiplasmodial activity of dobinin K in vitro and study its acting mechanism. The antiplasmodial activity of dobinin K in vitro was evaluat...

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Veröffentlicht in:Molecules (Basel, Switzerland) Switzerland), 2024-10, Vol.29 (19), p.4759
Hauptverfasser: Sun, He, Liu, Bo-Chao, He, Long-Fei, Xiao, Chao-Jiang, Jiang, Bei, Shen, Lei
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Sprache:eng
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Zusammenfassung:Dobinin K is a novel eudesmane sesquiterpenoids compound isolated from the root of and displays potential antiplasmodial activity in vivo. Here, we evaluate the antiplasmodial activity of dobinin K in vitro and study its acting mechanism. The antiplasmodial activity of dobinin K in vitro was evaluated by concentration-, time-dependent, and stage-specific parasite inhibition assay. The potential target of dobinin K on was predicted by transcriptome analysis. Apoptosis of was detected by Giemsa, Hoechst 33258, and TUNEL staining assay. The reactive oxygen species (ROS) level, oxygen consumption, and mitochondrial membrane potential of were assessed by DCFH-DA, R01, and JC-1 fluorescent dye, respectively. The effect of dobinin K on the mitochondrial electron transport chain (ETC) was investigated by enzyme activity analysis and the binding abilities of dobinin K with different enzymes were learned by molecular docking. Dobinin K inhibited the growth of in a concentration-, time-dependent, and stage-specific manner. The predicted mechanism of dobinin K was related to the redox system of . Dobinin K increased intracellular ROS levels of and induced their apoptosis. After dobinin K treatment, mitochondria lost their function, which was presented as decreased oxygen consumption and depolarization of the membrane potential. Among five dehydrogenases in ETC, dobinin K displayed the best inhibitory power on NDH2 activity. Our findings indicate that the antiplasmodial effect of dobinin K in vitro is mediated by the enhancement of the ROS level in and the disruption of its mitochondrial function.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules29194759