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Kastamonu Medical Journal regularly publishes internationally qualified issues in the field of Medicine in the light of up-to-date information.

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Original Article
The protective effect of chrysin against glutamate-induced oxidative stress and inflammation in SH-SY5Y cells
Aims: Chrysin is a flavonoid with economic value and medicinal effects commonly found in propolis, honey, and blue passion flowers. It has many pharmacological properties such as anticancer, antitumor, antioxidant, neurotrophic, and antidepressant. Glutamate plays an important role in brain functions; however, its high concentration in the central nervous system causes neurotoxic effects. This study aimed to investigate the effect of Chrysin on glutamate-induced cytotoxicity in SH-SY5Y neuroblastoma cells.
Methods: This study was conducted in 4 groups; control, Chrysin (50 µM), glutamate (10 mM), and glutamate+Chrysin. cell viability, total oxidant status (TOS), total antioxidant status (TAS), tumor necrosis factor alpha (TNF-a), and interleukin 1 ß (IL-1ß) levels in the cells were determined by ELISA kit.
Results: It is shown that glutamate application caused cytotoxicity in SH-SY5Y neuroblastoma cells and increased TOS, TNF-a, and IL-1ß levels. However, in SH-SY5Y cells treated with Chrysin before glutamate incubation, TOS, TNF-a, and IL-1ß levels decreased compared to the glutamate group, while TAS and cell viability levels increased.
Conclusion: Chrysin’s antioxidant properties played a protective role in SH-SY5Y cells against glutamate-induced increased oxidative stress and inflammation.


1. Ganai SA, Sheikh FA, Baba ZA. Plant flavone Chrysin as an emerging histone deacetylase inhibitor for prosperous epigenetic-based anticancer therapy. Phytother Res. 2021;35(2):823-834. doi:10.1002/ptr.6869
2. Farkhondeh T, Samarghandian S, Roshanravan B. Impact of Chrysin on the molecular mechanisms underlying diabetic complications. J Cell Physiol. 2019;234(10):17144-17158. doi:10.1002/jcp.28488
3. Gao S, Siddiqui N, Etim I, Du T, Zhang Y, Liang D. Developing nutritional component Chrysin as a therapeutic agent: bioavailability and pharmacokinetics consideration, and ADME mechanisms. Biomed Pharmacother. 2021;142:112080. doi:10.1016/j.biopha.2021.112080
4. Huo JF, Zhang ML, Wang XX, Zou DH. Chrysin induces osteogenic differentiation of human dental pulp stem cells. Exp Cell Res. 2021; 400(2):112466. doi:10.1016/j.yexcr.2020.112466
5. Kasala ER, Bodduluru LN, Madana RM, V AK, Gogoi R, Barua CC. Chemopreventive and therapeutic potential of Chrysin in cancer: mechanistic perspectives. Toxicol Lett. 2015;233(2):214-225. doi:10.1016/ j.toxlet.2015.01.008
6. Naz S, Imran M, Rauf A, et al. Chrysin: Pharmacological and therapeutic properties. Life Sci. 2019;235:116797. doi:10.1016/j.lfs.2019.116797
7. Newsholme P, Procopio J, Lima MM, Pithon-Curi TC, Curi R. Glutamine and glutamate-their central role in cell metabolism and function. Cell Biochem Funct. 2003;21(1):1-9. doi:10.1002/cbf.1003
8. Sonnewald U, Schousboe A. Introduction to the glutamate-glutamine cycle. The glutamate/GABA-glutamine cycle: amino acid neurotransmitter homeostasis. Adv. Neurobiol. 2016;1-7.
9. Heath PR, Shaw PJ. Update on glutamatergic neurotransmitter system and the role of excitotoxicity in amyotrophic lateral sclerosis. Muscle Nerve. 2002;26(4):438-458. doi:10.1002/mus.10186
10. Uğuz AC, Öz A, Nazıroğlu M. Curcumin inhibits apoptosis by regulating intracellular calcium release, reactive oxygen species and mitochondrial depolarization levels in SH-SY5Y neuronal cells. J Recept Signal Transduct Res. 2016;36(4):395-401. doi:10.3109/10799893.2015.1108337
11. Darendelioglu, E. Neuroprotective effects of Chrysin on diclofenac-induced apoptosis in SH-SY5Y cells. Neurochem Res. 2020;45(5):1064-1071. doi:10.1007/s11064-020-02982-8
12. Yang SJ, Han AR, Kim EA, et al. KHG21834 attenuates glutamate-induced mitochondrial damage, apoptosis, and NLRP3 inflammasome activation in SH-SY5Y human neuroblastoma cells. Eur J Pharmacol. 2019;856:172412. doi:10.1016/j.ejphar.2019.172412
13. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-254. doi:10.1016/0003-2697(76) 90527-3
14. Todd AC, Hardingham GE. The regulation of astrocytic glutamate transporters in health and neurodegenerative diseases. Int J Mol Sci. 2020;21(24):9607. doi:10.3390/ijms21249607
15. Arundine M, Tymianski M. Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury. Cell Mol Life Sci. 2004;61(6):657-668. doi:10.1007/s00018-003-3319-x
16. Shen Z, Xiang M, Chen C, et al. Glutamate excitotoxicity: potential therapeutic target for ischemic stroke. Biomed Pharmacother. 2022;151: 113125. doi:10.1016/j.biopha.2022.113125
17. Doğan, M, Yıldızhan, K. Investigation of the effect of paracetamol against glutamate-induced cytotoxicity in C6 glia cells. Cumhuriyet Sci J. 202;42(4):789-794. doi:10.17776/csj.999199
18. Kasala ER, Bodduluru LN, Madana RM, V AK, Gogoi R, Barua CC. Chemopreventive and therapeutic potential of Chrysin in cancer: mechanistic perspectives. Toxicol Lett. 2015;233(2):214-225. doi:10.1016/ j.toxlet.2015.01.008
19. Ayna A, Özbolat SN, Darendelioglu E. Quercetin, Chrysin, caffeic acid and ferulic acid ameliorate cyclophosphamide-induced toxicities in SH-SY5Y cells. Mol Biol Rep. 2020;47(11):8535-8543. doi:10.1007/s11033-020-05896-4
20. Özbolat SN, Ayna A. Chrysin suppresses HT-29 cell death induced by diclofenac through apoptosis and oxidative damage. Nutr Cancer. 2021; 73(8):1419-1428. doi:10.1080/01635581.2020.1801775
21. Çetindağ Çiltaş A, Gündoğdu S, Yulak F. Levetiracetam protects against glutamate-ınduced excitotoxicity in SH-SY5Y cell line. Int J Nature Life Sci. 2022;6(2):142-150. doi:10.47947/ijnls.1187054
22. Çiçek A, Hacımüftüoğlu A, Taghızadehghalehjoughı T. The study of pycegeneol provtive effect on glumate induced neurotoxicity: in vitro evolation. Erzincan Univ J Sci Technol. 2021;14(2):864-873.
23. Smith T, Groom A, Zhu B, Turski L. Autoimmune encephalomyelitis ameliorated by AMPA antagonists. Nat Med. 2000;6(1):62-66. doi:10. 1038/71548
24. Jang DI, Lee AH, Shin HY, et al. The role of tumor necrosis factor alpha (TNF-α) in autoimmune disease and current TNF-α inhibitors in therapeutics. Int J Mol Sci. 2021;22(5):2719. doi:10.3390/ijms22052719
25. Fischer R, Maier O. Interrelation of oxidative stress and inflammation in neurodegenerative disease: role of TNF. Oxid Med Cell Longev. 2015; 2015:610813. doi:10.1155/2015/610813
26. Liu S, Yin T, Wei X, et al. Downregulation of adiponectin induced by tumor necrosis factor alpha is involved in the aggravation of posttraumatic myocardial ischemia/reperfusion injury. Crit Care Med. 2011;39(8):1935-1943.
27. Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci. 2009;29(43):13435-13444. doi:10.1523/JNEUROSCI.3257-09.2009
28. Chaparro-Huerta V, Flores-Soto ME, Gudiño-Cabrera G, Rivera-Cervantes MC, Bitzer-Quintero OK, Beas-Zárate C. Role of p38 MAPK and pro-inflammatory cytokines expression in glutamate-induced neuronal death of neonatal rats. Int J Dev Neurosci. 2008;26(5):487-495. doi:10.1016/j.ijdevneu.2008.02.008
29. Mizuno T, Zhang G, Takeuchi H,et al. Interferon-gamma directly induces neurotoxicity through a neuron specific, calcium-permeable complex of IFN-gamma receptor and AMPA GluR1 receptor. FASEB J. 2008;22(6):1797-1806. doi:10.1096/fj.07-099499
30. Ahlatcı A, Yıldızhan K, Tülüce Y, Bektaş M. Valproic acid attenuated PTZ-induced oxidative stress, inflammation, and apoptosis in the SH-SY5Y cells via modulating the TRPM2 channel. Neurotox Res. 2022; 40(6):1979-1988. doi:10.1007/s12640-022-00622-3
31. Carson MJ, Doose JM, Melchior B, Schmid CD, Ploix CC. CNS immune privilege: hiding in plain sight. Immunol Rev. 2006;213:48-65. doi:10. 1111/j.1600-065X.2006.00441.x
32. Eldutar E, Kandemir FM, Kucukler S, Caglayan C. Restorative effects of Chrysin pretreatment on oxidant-antioxidant status, inflammatory cytokine production, and apoptotic and autophagic markers in acute paracetamol-induced hepatotoxicity in rats: an experimental and biochemical study. J Biochem Mol Toxicol. 2017;31(11):10.1002/jbt.21960. doi:10.1002/jbt.21960
33. Izuta H, Shimazawa M, Tazawa S, Araki Y, Mishima S, Hara H. Protective effects of Chinese propolis and its component, chrysin, against neuronal cell death via inhibition of mitochondrial apoptosis pathway in SH-SY5Y cells. J Agric Food Chem. 2008;56(19):8944-8953. doi:10.1021/jf8014206
34. Anand KV, Anandhi R, Pakkiyaraj M, Geraldine P. Protective effect of chrysin on carbon tetrachloride (CCl4)-induced tissue injury in male Wistar rats. Toxicol Ind Health. 2011;27(10):923-933. doi:10.1177/ 0748233711399324
35. Ye B, Ling W, Wang Y, Jaisi A, Olatunji OJ. Protective effects of chrysin against cyclophosphamide-induced cardiotoxicity in rats: a biochemical and histopathological approach. Chem Biodivers. 2022;19(3):e202100 886. doi:10.1002/cbdv.202100886 </ol> <p>
Volume 5, Issue 3, 2025
Page : 166-171
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