İrem Gülfem ALBAYRAK, Seda KUŞOĞLU GÜLTEKİN, Muhsin KONUK

Effect of Melaleuca alternifolia oil on cytotoxicity and neuropeptide y gene expression

Background and Aims: This study aims to investigate the effect of tea tree oil (TTO), which is an oil produced by steam distil- lation of the Melaleuca alternifolia (Maiden & Betche) Cheel plant terminal branches and leaves, on changes in neuropeptide Y (NPY) gene expression in SH-SY5Y neuroblastoma cells. Methods: The first stage of this study investigates the cytotoxic/proliferative effects of TTO solutions prepared at different concentrations on the SH-SY5Y cell line using the tetrazolium reduction (MTT) assay. The next stage analyzes the effects of the determined TTO concentrations on NPY gene expression using the real-time polymerase chain reaction (qPCR) method. Results: TTO concentrations prepared at a ratio of 1:32, 1:64, and 1:28 (v/v) showed statistically significant effects on cells in the cytotoxicity test and were used in the gene expression analysis. The highest significant gene expression change was seen in the cells in which the TTO solution had been applied at a ratio of 1:64 for 24 hours. NPY gene expression in these cells was determined to have increased 2.24 times compared to control cells. Conclusion: Upon evaluating the results from the MTT assay and gene expression analysis, the solutions of the cells prepared at different TTO ratios were determined to have caused changes in gene expression. Future studies will be able to reveal all affected molecular pathways by increasing research involving TTO.

Keywords:

Gene expression, neuroblastoma NPY, SH-SY5Y, tea tree oil,

PDF

___

Álvaro, A.R., Rosmaninho-Salgado, J., Santiago, A.R., Martins, J., Aveleira, C., Santos, P.F., Pereira, T., Gouveia, D., Carvalho, A.L., Grouzmann, E., Ambrósio, A.F., Cavadas, C. (2007). NPY in rat retina is present in neurons, in endothelial cells and also in microglial and Müller cells. Neurochemistry International, 50(5), 757–763. https://doi.org/10.1016/J.NEUINT.2007.01.010
Arcella, A., & Sanchez, M. (2021). Natural substances to potentiate canonical glioblastoma chemotherapy. Journal of Chemotherapy, 33(5), 276-287. https://doi.org/10.1080/1120009X.2021.1873633
Atkinson, N., & Brice, H.E. (1955). Antibacterial substances pro- duced by flowering plants. II. The antibacterial action of essential oils from some Australian plants. The Australian Journal of Experi- mental Biology and Medical Science, 33(5), 547–554. https://doi. org/10.1038/icb.1955.56
Bao, Y., Wang, W., Zhou, Z., & Sun, C. (2014). Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer pre- vention. PLoS ONE, 9(12), 114764. https://doi.org/10.1371/journal. pone.0114764
Barnea, A., Roberts, J., Keller, P., & Word, R.A. (2001). Interleukin- 1β induces expression of neuropeptide Y in primary astrocyte cultures in a cytokine-specific manner: induction in human but not rat astrocytes. Brain Research, 896(1–2), 137–145. https://doi. org/10.1016/S0006-8993(01)02141-2
Carson, C.F., Hammer, K.A., & Riley, T.V. (2006). Melaleuca alterni- folia (tea tree) oil: A review of antimicrobial and other medicinal properties. Clinical Microbiology Reviews, 19, 50–62. https://doi. org/10.1128/CMR.19.1.50-62.2006
Duarte-Neves, J., Pereira de Almeida, L., & Cavadas, C. (2016). Neuropeptide Y (NPY) as a therapeutic target for neurodegen- erative diseases. Neurobiology of Disease, 95, 210–224. https://doi. org/10.1016/J.NBD.2016.07.022
Farrelly, L.A., Savage, N.T.P., O’Callaghan, C., Toulouse, A., & Yilma- zer-Hanke, D.M. (2013). Therapeutic concentrations of valproate but not amitriptyline increase neuropeptide Y (NPY) expression in the human SH-SY5Y neuroblastoma cell line. Regulatory Pep- tides, 186, 123–130. https://doi.org/10.1016/j.regpep.2013.08.005
Fendt, M., & Fanselow, M.S. (1999). The neuroanatomical and neurochemical basis of conditioned fear. Neuroscience & Biobe- havioral Reviews, 23(5), 743–760. https://doi.org/10.1016/S0149-7634(99)00016-0
Ferreira, R., Xapelli, S., Santos, T., Silva, A.P., Cristóvão, A., Cortes, L., & Malva, J.O. (2010). Neuropeptide Y Modulation of Interleukin- 1β (IL-1β)-induced Nitric Oxide Production in Microglia. Jour- nal of Biological Chemistry, 285(53), 41921–41934. https://doi. org/10.1074/JBC.M110.164020
Hayes, D.P. (2007). Nutritional hormesis. European Journal of Clini- cal Nutrition, 61, 147–159. https://doi.org/10.1038/sj.ejcn.1602507
Heilig, M. (2004). The NPY system in stress, anxiety and depres- sion. Neuropeptides, 38(4), 213–224. https://doi.org/10.1016/J. NPEP.2004.05.002
Heilig, M., & Murison, R. (1987). Intracerebroventricular neuropep- tide Y protects against stress-induced gastric erosion in the rat. European Journal of Pharmacology, 137(1), 127–129. https://doi. org/10.1016/0014-2999(87)90191-9
Inouye, S., Tsuruoka, T., Watanabe, M., Takeo, K., Akao, M., Nishiya- ma, Y., & Yamaguchi, H. (2000). Inhibitory effect of essential oils on apical growth of Aspergillus fumigatus by vapour contact. Mycoses, 43(1–2), 17–23. https://doi.org/10.1046/j.1439-0507.2000.00538.x
Inouye, S., Uchida, K., & Yamaguchi, H. (2001). In-vitro and in- vivo anti-Trichophyton activity of essential oils by vapour contact. Mycoses, 44(3–4), 99–107. https://doi.org/10.1046/j.1439- 0507.2001.00618.x
Inouye, Watanabe, M., Nishiyama, Y., Takco, K., Akao, M., & Ya- maguchi, H. (1998). Antisporulating and respiration-inhibitory effects of essential oils on filamentous fungi. Mycoses, 41(9–10), 403–410. https://doi.org/10.1111/j.1439-0507.1998.tb00361.x
Kaya, B., Atasever-Arslan, B., Kalkan, Z., Gür, H., & Ülküseven, B. (2016). Apoptotic mechanisms of nickel(II) complex with N1acet- ylacetone-N4- 4-methoxy-salicylidene-S-allyl-thiosemicarbazone on HL60 leukemia cells. General Physiology and Biophysics, 35(4), 451–458. https://doi.org/10.4149/GPB_2016006A
Khan, S.A., McLean, M. K., & Slater, M.R. (2013). Concentrated tea tree oil toxicosis in dogs and cats: 443 cases (2002-2012). Jour- nal of the American Veterinary Medical Association, 244(1), 95–99. https://doi.org/10.2460/javma.244.1.95
Kitlinska, J. (2007). Neuropeptide Y (NPY) in neuroblastoma: Effect on growth and vascularization. Peptides, 28(2), 405–412. https:// doi.org/10.1016/J.PEPTIDES.2006.08.038
Kumari, P. (2013). Antimicrobial properties of tea tree oil. Interna- tional Journal of Bioinformatics and Biological Science, 1(1), 71–77.
Low, D., Rawal, B.D., & Griffin, W.J. (1974). Antibacterial action of the essential oils of some Australian myrtaceae with special references to the activity of chromatographic fractions of oil of Eucalyptus citriodora. Planta Medica, 26(2), 184–189. https://doi. org/10.1055/s-0028-1097987
Morris, M.C., Donoghue, A., Markowitz, J.A., & Osterhoudt, K.C. (2003). Ingestion of tea tree oil (Melaleuca oil) by a 4-year- old boy. Pediatric Emergency Care, 19(3), 169–171. https://doi. org/10.1097/01.pec.0000081241.98249.7b
Naveilhan, P., Canals, J.M., Valjakka, A., Vartiainen, J., Arenas, E., & Ernfors, P. (2001). Neuropeptide Y alters sedation through a hypothalamic Y1-mediated mechanism. European Journal of Neuroscience, 13(12), 2241–2246. https://doi.org/10.1046/j.0953- 816X.2001.01601.x
Redrobe, J. P., Dumont, Y., Fournier, A., & Quirion, R. (2002). The neuropeptide Y (NPY) Y1 receptor subtype mediates NPY-in- duced antidepressant-like activity in the mouse forced swim- ming test. Neuropsychopharmacology, 26(5), 615–624. https://doi. org/10.1016/S0893-133X(01)00403-1
Sajdyk, T.J., Vandergriff, M.G., & Gehlert, D.R. (1999). Amygdalar neuropeptide Y Y1 receptors mediate the anxiolytic-like actions of neuropeptide Y in the social interaction test. European Jour- nal of Pharmacology, 368(2–3), 143–147. https://doi.org/10.1016/ S0014-2999(99)00018-7
Silva, A.P., Cavadas, C., & Grouzmann, E. (2002). Neuropeptide Y and its receptors as potential therapeutic drug targets. Clinica Chimica Acta; International Journal of Clinical Chemistry, 326(1–2), 3–25. https://doi.org/10.1016/S0009-8981(02)00301-7
Stogner, K.A., & Holmes, P.V. (2000). Neuropeptide-Y exerts anti- depressant-like effects in the forced swim test in rats. European Journal of Pharmacology, 387(2), R9–R10. https://doi.org/10.1016/ S0014-2999(99)00800-6
Villar, D., Knight, M.J., Hansen, S.R., & Buck, W.B. (1994, April 1). Tox- icity of melaleuca oil and related essential oils applied topically on dogs and cats. Veterinary and Human Toxicology, 36, 139–142. Retrieved from https://europepmc.org/article/med/8197716
Wang, D., Calabrese, E.J., Lian, B., Lin, Z., & Calabrese, V. (2018, April 1). Hormesis as a mechanistic approach to understanding herbal treatments in traditional Chinese medicine. Pharmacol- ogy and Therapeutics, 184, 42–50. https://doi.org/10.1016/j.phar- mthera.2017.10.013