Parasites, Hosts and Diseases

  • 제62권2호
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  • Pages.169-179
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  • 2024
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  • 2982-5164(pISSN)
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  • 1738-0006(eISSN)
대한기생충학·열대의학회 (The Korea Society for Parasitology and Tropical Medicine)
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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)
  • 투고 : 2023.10.16
  • 심사 : 2024.02.14
  • 발행 : 2024.05.31
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초록

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.

키워드

과제정보

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

참고문헌

  1. Schuster FL, Visvesvara GS. Free-living amoebae as opportunistic and non-opportunistic pathogens of humans and animals. Int J Parasitol 2004;34(9):1001-1027. https://doi.org/10.1016/j.ijpara.2004.06.004 
  2. Gharpure R, Bliton J, Goodman A, Ali IKM, Yoder J, et al. Epidemiology and clinical characteristics of primary amebic meningoencephalitis caused by Naegleria fowleri: a global review. Clin Infect Dis 2021;73(1):e19-e27. https://doi.org/10.1093/cid/ciaa520 
  3. Gharpure R, Gleason M, Salah Z, Blackstock AJ, Hess-Homeier D, et al. Geographic range of recreational water-associated primary amebic meningoencephalitis, United States, 1978-2018. Emerg Infect Dis 2021;27(1):271-274. https://doi.org/10.3201/eid2701.202119 
  4. Baig AM, Khan NA. Novel chemotherapeutic strategies in the management of primary amoebic meningoencephalitis due to Naegleria fowleri. CNS Neurosci Ther 2014;20(3):289-290. https://doi.org/10.1111/cns.12225 
  5. Haston JC, Cope JR. Amebic encephalitis and meningoencephalitis: an update on epidemiology, diagnostic methods, and treatment. Curr Opin Infect Dis 2023;36(3):186-191. https://doi.org/10.1097/QCO.0000000000000923 
  6. Boonhok R, Sangkanu S, Norouzi R, Siyadatpanah A, Mirzaei F, et al. Amoebicidal activity of Cassia angustifolia extract and its effect on Acanthamoeba triangularis autophagy-related gene expression at the transcriptional level. Parasitology 2021;148(9):1074-1082. https://doi.org/10.1017/S0031182021000718 
  7. Mitsuwan W, Sangkanu S, Romyasamit C, Kaewjai C, Jimoh TO, et al. Curcuma longa rhizome extract and curcumin reduce the adhesion of Acanthamoeba triangularis trophozoites and cysts in polystyrene plastic surface and contact lens. Int J Parasitol Drugs Drug Resist 2020;14:218-229. https://doi.org/10.1016/j.ijpddr.2020.11.001 
  8. Belofsky G, Carreno R, Goswick SM, John DT. Activity of isoflavans of Dalea aurea (Fabaceae) against the opportunistic ameba Naegleria fowleri. Planta Med 2006;72(2):383-386. https://doi.org/10.1055/s-2005-9162529. 
  9. Le HG, Choi JS, Hwang BS, Jeong YT, Kang JM, et al. Phragmites australis (Cav.) Trin. ex Steud. extract induces apoptosislike programmed cell death in Acanthamoeba castellanii trophozoites. Plants 2022;11(24):3459. https://doi.org/10.3390/plants11243459 
  10. Siddiqui R, Boghossian A, Khatoon B, Kawish M, Alharbi AM, et al. Anti-amoebic properties of metabolites against Naegleria fowleri and Balamuthia mandrillaris. Antibiotics 2022;11(5):539. https://doi.org/10.3390/antibiotics11050539 
  11. Le HG, Kang JM, Vo TC, Na BK. Kaempferol induces programmed cell death in Naegleria fowleri. Phytomedicine 2023; 119:154994. https://doi.org/10.1016/j.phymed.2023.154994 
  12. Choung HL, Hong SK. Distribution patterns, floristic differentation and succession of Pinus densiflora forest in South Korea: a perspective at nation-wide scale. Phytocoenologia 2006;36(2):213229. https://doi.org/10.1127/0340-269X/2006/0036-0213 
  13. Jung MJ, Chung HY, Choi JH, Choi JS. Antioxidant principles from the needles of red pine, Pinus densiflora. Phytother Res 2003;17(9):1064-1068. https://doi.org/10.1002/ptr.1302 
  14. Suntar I, Tumen I, Ustun O, Keles H, Kupeli Akkol E. Appraisal on the wound healing and anti-inflammatory activities of the essential oils obtained from the cones and needles of Pinus species by in vivo and in vitro experimental models. J Ethnopharmacol 2012;139(2):533-540. https://doi.org/10.1016/j.jep.2011.11.045 
  15. Wu Y, Bai J, Zhong K, Huang Y, Qi H, Jiang Y, et al. Antibacterial activity and membrane-disruptive mechanism of 3-p-transcoumaroyl-2-hydroxyquinic acid, a novel phenolic compound from pine needles of Cedrus deodara, against Staphylococcus aureus. Molecules 2016;21(8):1084. https://doi.org/10.3390/molecules21081084 
  16. Jo JR, Park JS, Park YK, Chae YZ, Lee GH, et al. Pinus densiflora leaf essential oil induces apoptosis via ROS generation and activation of caspases in YD-8 human oral cancer cells. Int J Oncol 2012;40(4):1238-1245. https://doi.org/10.3892/ijo.2011.1263 
  17. Sang JL, Ki WL, Haeng JH, Ji YC, Seo YK, et al. Phenolic phytochemicals derived from red pine (Pinus densiflora) inhibit the invasion and migration of SK-Hep-1 human hepatocellular carcinoma cells. Ann N Y Acad Sci 2007;1095:536-544. https://doi.org/10.1196/annals.1397.058 
  18. Park J, Kim WJ, Kim W, Park C, Choi CY, et al. Antihypertensive effects of dehydroabietic and 4-epi-trans-communic acid isolated from Pinus densiflora. J Med Food 2021;24(1):50-58. https://doi.org/10.1089/jmf.2020.4797 
  19. Park J, Lee B, Choi H, Kim W, Kim HJ, et al. Antithrombosis activity of protocatechuic and shikimic acids from functional plant Pinus densiflora Sieb. et Zucc needles. J Nat Med 2016;70(3):492-501. https://doi.org/10.1007/s11418-015-0956-y 
  20. Wang L, Feng Z, Wang X, Wang X, Zhang X. DEGseq: an R package for identifying differentially expressed genes from RNA-seq data. Bioinformatics 2010;26(1):136-138. https://doi.org/10.1093/bioinformatics/btp612 
  21. Le HG, Ham AJ, Kang JM, Vo TC, Naw H, et al. A novel cysteine protease inhibitor of Naegleria fowleri that is specifically expressed during encystation and at mature cysts. Pathogens 2021;10(4):388. https://doi.org/10.3390/pathogens10040388 
  22. Adams J, Kelso R, Cooley L. The kelch repeat superfamily of proteins: propellers of cell function. Trends Cell Biol 2000;10(1):17-24. https://doi.org/10.1016/s0962-8924(99)01673-6 
  23. Stirnimann CU, Petsalaki E, Russell RB, Muller CW. WD40 proteins propel cellular networks. Trends Biochem Sci 2010;35(10):565-574. https://doi.org/10.1016/j.tibs.2010.04.003 
  24. Leonard TA, Hurley JH. Regulation of protein kinases by lipids. Curr Opin Struct Biol 2011;21(6):785-791. https://doi.org/10.1016/j.sbi.2011.07.006 
  25. Mosavi LK, Cammett TJ, Desrosiers DC, Peng Z. The ankyrin repeat as molecular architecture for protein recognition. Protein Sci 2004;13(6):14351448. https://doi.org/10.1110/ps.03554604 
  26. Stark Z, Bruno DL, Mountford H, Lockhart PJ, Amor DJ. De novo 325 kb microdeletion in chromosome band 10q25.3 including ATRNL1 in a boy with cognitive impairment, autism and dysmorphic features. Eur J Med Genet 2010;53(5):337-339. https://doi.org/10.1016/j.ejmg.2010.07.009 
  27. Miller EN, Jarboe LR, Yomano LP, York SW, Shanmugam KT, et al. Silencing of NADPH-dependent oxidoreductase genes (yqhD and dkgA) in furfural-resistant ethanologenic Escherichia coli. Appl Environ Microbiol 2009;75(13):4315-4323. https://doi.org/10.1128/AEM.00567-09 
  28. Karlsson CMG, Cerro-Galvez E, Lundin D, Karlsson C, VilaCosta M, et al. Direct effects of organic pollutants on the growth and gene expression of the baltic sea model bacterium Rheinheimera sp. BAL341. Microb Biotechnol 2019;12(5):892-906. https://doi.org/10.1111/1751-7915.13441 
  29. Alvarez-Carreno C, Alva V, Becerra A, Lazcano A. Structure, function and evolution of the hemerythrin-like domain superfamily. Protein Sci 2018;27(4):848-860. https://doi.org/10.1002/pro.3374 
  30. Asai DJ, Wilkes DE. The dynein heavy chain family. J Eukaryot Microbiol 2004;51(1):23-29. https://doi.org/10.1111/j.1550-7408.2004.tb00157.x 
  31. Sumimoto H, Kamakura S, Ito T. Structure and function of the PB1 domain, a protein interaction module conserved in animals, fungi, amoebas, and plants. Sci STKE 2007;2007(401):re6. https://doi.org/10.1126/stke.4012007re6 
  32. Trimbur GM, Walsh CJ. BN46/51, a new nucleolar protein, binds to the basal body region in Naegleria gruberi flagellates. J Cell Sci 1992;103(1):167-181. https://doi.org/10.1242/jcs.103.1.167