Accumulating evidences demonstrated that Reactive Oxygen Species (ROS) may lead to serious damages to numerous cellular biomolecules, consequently resulting in the development of several neurological diseases. Diclofenac (Dic), the most widely preferred non-steroidal anti-inflammatory drug (NSAID) induces apoptosis by an alteration in function of mitochondria and creation of ROS. Chrysin (Chr) is a naturally active component that is found in numerous plants and bee products and retains strong neuroprotective and antioxidant properties. However its effect of Dic induced injury on SH-SY5Y neuron cells have not been investigated to date. The goal of present research was to study the molecular mechanisms of Chr protection from oxidative injury caused by Dic in SH-SY5Y cells. Dic induced significant toxicity on the cells and this effect was reversed by pre-treatment with Chr. Dic triggered a noteworthy increase in the cellular ROS and Lipid peroxidation (LPO) levels and decrease in Total antioxidant status (TAS) level while pre-treatment with Chr reversed these effects. Dic induction increased the Bax, cytochrome c, cas-3, cas-8 and p53 expression at gene transcription level. Elevated levels of these genes considerably decreased by Chr pre-treatment revealing the defensive effects of Chr. The results obviously presented that exposure of SH-SY5Y with Dic resulted in oxidative stress and apoptosis while pre-treatment of neuron cells with Chr protects the cells against apoptosis triggered by Dic induction.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Darendelioglu E, Aykutoglu G, Tartik M, Baydas G (2016) Turkish propolis protects human endothelial cells in vitro from homocysteine-induced apoptosis. Acta Histochem 118(4):369–376
Santos AL, Sinha S, Lindner AB (2018) The good, the bad, and the ugly of ROS: new insights on aging and aging-related diseases from eukaryotic and prokaryotic model organisms. Oxid Med Cell Longev. https://doi.org/10.1155/2018/1941285
Giorgi C, Marchi S, Simoes IC, Ren Z, Morciano G, Perrone M, Szymański J (2018) Mitochondria and reactive oxygen species in aging and age-related diseases. Int Rev Cell Mol Biol 340:209–344
Liu Z, Ren Z, Zhang J, Chuang CC, Kandaswamy E, Zhou T, Zuo L (2018) Role of ROS and nutritional antioxidants in human diseases. Front Physiol 9:477
Sik KS et al (2004) Neuroprotective effects of flavones on hydrogen peroxide-induced apoptosis in SH-SY5Y neuroblostoma cells. Bioorg Med Chem Lett 14(9):2261–2264
Klein JA, Ackerman SL (2003) Oxidative stress, cell cycle, and neurodegeneration. J Clin Investig 111(6):785–793
Jenner P (2003) Oxidative stress in Parkinson's disease. Ann Neurol 53(S3):S26–S38
McGettigan P, Henry D (2013) Use of non-steroidal anti-inflammatory drugs that elevate cardiovascular risk: an examination of sales and essential medicines lists in low-, middle-, and high-income countries. PLoS Med 10(2):e1001388
Gómez-Lechón MJ, Ponsoda X, O'Connor E, Donato T, Jover R, Castell JV (2003) Diclofenac induces apoptosis in hepatocytes. Toxicol In Vitro 17(5–6):675–680
Tsutsumi S, Gotoh T, Tomisato W, Mima S, Hoshino T, Hwang HJ, Mizushima T (2004) Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis. Cell Death Differ 11(9):1009
Simon HU, Haj-Yehia A, Levi-Schaffer F (2000) Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 5(5):415–418
Issaeva N (2019). p53 Signaling in Cancers.
Pietta PG (2000) Flavonoids as antioxidants. J Nat Prod 63(7):1035–1042
Mittler R (2002) Oxidative stress, antioxidants and stress tolerance. Trends Plant Sci 7(9):405–410
Sies H (1997) Oxidative stress: oxidants and antioxidants. Exp Physiol 82(2):291–295
Shahidi F, Janitha PK, Wanasundara PD (1992) Phenolic antioxidants. Crit Rev Food Sci Nutr 32(1):67–103
Fishkin RJ, Winslow JT (1997) Endotoxin-induced reduction of social investigation by mice: interaction with amphetamine and anti-inflammatory drugs. Psychopharmacology 132(4):335–341
Habtemariam S (1997) Flavonoids as inhibitors or enhancers of the cytotoxicity of tumor necrosis factor-α in L-929 tumor cells. J Nat Prod 60(8):775–778
Chaudhuri S, Banerjee A, Basu K, Sengupta B, Sengupta PK (2007) Interaction of flavonoids with red blood cell membrane lipids and proteins: antioxidant and antihemolytic effects. Int J Biol Macromol 41(1):42–48
Vauzour D, Vafeiadou K, Rodriguez-Mateos A, Rendeiro C, Spencer JP (2008) The neuroprotective potential of flavonoids: a multiplicity of effects. Genes Nutr 3(3):115
Zhang G, Chen X, Guo J, Wang J (2009) Spectroscopic investigation of the interaction between chrysin and bovine serum albumin. J Mol Struct 921(1–3):346–351
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358
Mukherjee B, Mahapatra S, Das S, Roy G, Dey S (2006) HPLC detection of plasma concentrations of diclofenac in human volunteers administered with povidone-ethyl cellulose based experimental transdermal matrix-type patches. Methods Find Exp Clin Pharmacol 28(5):301–306
Tang W (2003) The metabolism of diclofenac-enzymology and toxicology perspectives. Curr Drug Metab 4(4):319–329
Boelsterli UA (2003) Diclofenac-induced liver injury: a paradigm of idiosyncratic drug toxicity. Toxicol Appl Pharmacol 192(3):307–322
El Khashab IH, Abdelsalam RM, Elbrairy AI, Attia AS (2019) Chrysin attenuates global cerebral ischemic reperfusion injury via suppression of oxidative stress, inflammation and apoptosis. Biomed Pharmacother 112:108619
Sidoti-de Fraisse C, Rincheval V, Risler Y, Mignotte B, Vayssi`ere JL, (1998) TNF-α activates at least two apoptotic signaling cascades. Oncogene 17(13):1639–2165
Kusuhara H, Komatsu H, Sumichika H, Sugahara K (1999) Reactive oxygen species are involved in the apoptosis induced by nonsteroidal anti-inflammatory drugs in cultured gastric cells. Eur J Pharmacol 383(3):331–337
Hickey EJ, Raje RR, Reid VE, Gross SM, Ray SD (2001) Diclofenac induced in vivo nephrotoxicity may involve oxidative stress-mediatedmassive genomic DNA fragmentation and apoptotic cell death”. Free Radical Biol Med 31(2):139–152
El-Sisi AE, El-Sayad ME, Abdelsalam NM (2017) Protective effects of mirtazapine and chrysin on experimentally induced testicular damage in rats. Biomed Pharmacother 95:1059–1066
Reed JC (2001) Apoptosis-regulating proteins as targets for drug discovery. Trends Mol Med 7(7):314–319
Stennicke HR, Jürgensmeier JM, Shin H, Deveraux Q, Wolf BB, Yang X, Green DR (1998) Pro-caspase-3 is a major physiologic target of caspase-8. J Biol Chem 273(42):27084–27090
Mantawy EM, Esmat A, El-Bakly WM, ElDin RAS, El-Demerdash E (2017) Mechanistic clues to the protective effect of chrysin against doxorubicin-induced cardiomyopathy: Plausible roles of p53 MAPK, and AKT pathways. Sci Rep 7(1):4795
Earnshaw WC, Martins LM, Kaufmann SH (1999) Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 68(1):383–424
Bal-Price A, Guy CB (2000) Nitric-oxide-induced necrosis and apoptosis in PC12 cells mediated by mitochondria. J Neurochem 75(4):1455–1464
Buckley CD, Pilling D, Henriquez NV, Parsonage G, Threlfall K, Scheel-Toellner D et al (1999) RGD peptides induce apoptosis by direct caspase-3 activation. Nature 397(6719):534–539
Andoh T, Chock PB, Chiueh CC (2002) The roles of thioredoxin in protection against oxidative stress-induced apoptosis in SH-SY5Y cells. J Biol Chem 277(12):9655–9660
Procházková D, Boušová I, Wilhelmová N (2011) Antioxidant and prooxidant properties of flavonoids. Fitoterapia 82(4):513–523
Ryu S, Lim W, Bazer FW, Song G (2017) Chrysin induces death of prostate cancer cells by inducing ROS and ER stress. J Cell Physiol 232(12):3786–3797
Kasala ER, Bodduluru LN, Barua CC, Gogoi R (2015) Chrysin and its emerging role in cancer drug resistance. Chem Biol Interact 236:7–8
Tsuji PA, Walle T (2008) Cytotoxic effects of the dietary flavones chrysin and apigenin in a normal trout liver cell line. Chem Biol Interact 171(1):37–44
Kandhare AD, Shivakumar V, Rajmane A, Ghosh P, Bodhankar SL (2014) Evaluation of the neuroprotective effect of chrysin via modulation of endogenous biomarkers in a rat model of spinal cord injury. J Nat Med 68(3):586–603
Samarghandian S, Azimi Nezhad M, Mohammadi G (2014) Role of caspases, Bax and Bcl-2 in chrysin-induced apoptosis in the A549 human lung adenocarcinoma epithelial cells. Anti-Cancer Agents Med Chem 14(6):901–909
The author would like to thank the head of the Molecular Biology and Genetics department and the directorate of Central Research Laboratory of the Bingol University for their laboratory facilities.
Conflict of interest
The author declares that he has no conflict of interest.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Darendelioglu, E. Neuroprotective Effects of Chrysin on Diclofenac-Induced Apoptosis in SH-SY5Y Cells. Neurochem Res (2020). https://doi.org/10.1007/s11064-020-02982-8
- Oxidative stress