Kaempferol induces programmed cell death in Naegleria fowleri.

Autor: Lê HG; Department of Parasitology and Tropical Medicine, Institute of Health Science, Gyeongsang National University College of Medicine, Jinju 52727, Korea; Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, Korea., Kang JM; Department of Parasitology and Tropical Medicine, Institute of Health Science, Gyeongsang National University College of Medicine, Jinju 52727, Korea; Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, Korea., Võ TC; Department of Parasitology and Tropical Medicine, Institute of Health Science, Gyeongsang National University College of Medicine, Jinju 52727, Korea; Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, Korea., Na BK; Department of Parasitology and Tropical Medicine, Institute of Health Science, Gyeongsang National University College of Medicine, Jinju 52727, Korea; Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, Korea. Electronic address: bkna@gnu.ac.kr.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2023 Oct; Vol. 119, pp. 154994. Date of Electronic Publication: 2023 Jul 23.
DOI: 10.1016/j.phymed.2023.154994
Abstrakt: Background: Naegleria fowleri is a brain-eating amoeba causing a fatal brain infection called primary amoebic meningoencephalitis (PAM). Despite its high mortality over 95%, effective therapeutic drug for PAM has not been developed yet. Therefore, development of an effective and safe therapeutic drug for PAM is urgently needed. In this study, we investigated anti-amoebic effect of kaempferol (KPF) against N. fowleri and its underlying anti-amoebic molecular mechanisms.
Methods: Anti-amoebic activity of KPF against N. fowleri trophozoites, as well as cytotoxicity of KPF in C6 glial cells and CHO-K1 cells were investigated. The programmed cell death mechanisms in KPF-treated N. fowleri were also analyzed by apoptosis-necrosis assay, mitochondrial dysfunction assay, TUNEL assay, RT-qPCR, and CYTO-ID assay.
Results: KPF showed anti-amoebic activity against N. fowleri trophozoites with an IC 50 of 29.28 ± 0.63 μM. However, it showed no significant cytotoxicity to mammalian cells. KPF induced significant morphological alterations of the amoebae, resulting in death. Signals associated with apoptosis were detected in the amoebae upon treatment with KPF. KPF induced an increase of intracellular reactive oxygen species level, loss of mitochondrial membrane potential, increases of expression levels of genes associated with mitochondria dysfunction, and reduction of ATP levels in the amoebae. Autophagic vacuole accumulations with increased expression levels of autophagy-related genes were also detected in KPF-treated amoebae.
Conclusion: KPF induces programmed cell death in N. fowleri trophozoites via apoptosis-like pathway and autophagy pathway. KPF could be used as a candidate of anti-amoebic drug or supplement compound in the process of developing or optimizing therapeutic drug for PAM.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2023 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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