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The anti-amoebic activity of Pinus densiflora leaf extract against the brain-eating amoeba Naegleria fowleri

  • Huong Giang Le (Department of Parasitology and Tropical Medicine, Institute of Health Science, Gyeongsang National University College of Medicine) ;
  • Woong Kim (Department of Biomedical Science, Chosun University) ;
  • Jung-Mi Kang (Department of Parasitology and Tropical Medicine, Institute of Health Science, Gyeongsang National University College of Medicine) ;
  • Tuan Cuong Vo (Department of Parasitology and Tropical Medicine, Institute of Health Science, Gyeongsang National University College of Medicine) ;
  • Won Gi Yoo (Department of Parasitology and Tropical Medicine, Institute of Health Science, Gyeongsang National University College of Medicine) ;
  • Hyeonsook Cheong (Department of Biomedical Science, Chosun University) ;
  • Byoung-Kuk Na (Department of Parasitology and Tropical Medicine, Institute of Health Science, Gyeongsang National University College of Medicine)
  • Received : 2023.10.16
  • Accepted : 2024.02.14
  • Published : 2024.05.31

Abstract

Naegleria fowleri invades the brain and causes a fatal primary amoebic meningoencephalitis (PAM). Despite its high mortality rate of approximately 97%, an effective therapeutic drug for PAM has not been developed. Approaches with miltefosine, amphotericin B, and other antimicrobials have been clinically attempted to treat PAM, but their therapeutic efficacy remains unclear. The development of an effective and safe therapeutic drug for PAM is urgently needed. In this study, we investigated the anti-amoebic activity of Pinus densiflora leaf extract (PLE) against N. fowleri. PLE induced significant morphological changes in N. fowleri trophozoites, resulting in the death of the amoeba. The IC50 of PLE on N. fowleri was 62.3±0.95 ㎍/ml. Alternatively, PLE did not significantly affect the viability of the rat glial cell line C6. Transcriptome analysis revealed differentially expressed genes (DEGs) between PLE-treated and non-treated amoebae. A total of 5,846 DEGs were identified, of which 2,189 were upregulated, and 3,657 were downregulated in the PLE-treated amoebae. The DEGs were categorized into biological process (1,742 genes), cellular component (1,237 genes), and molecular function (846 genes) based on the gene ontology analysis, indicating that PLE may have dramatically altered the biological and cellular functions of the amoeba and contributed to their death. These results suggest that PLE has anti-N. fowleri activity and may be considered as a potential candidate for the development of therapeutic drugs for PAM. It may also be used as a supplement compound to enhance the therapeutic efficacy of drugs currently used to treat PAM.

Keywords

Acknowledgement

This research was supported by a National Research Foundation of Korea (NRF) grant from the Government of Korea (NRF-2021R1A2C1091855).

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