Polyphenols are natural antioxidants found in the human diet, which are known to have protective effects against neurodegenerative diseases by scavenging free radicals. Recently, combination therapies including cholinesterase (ChE) inhibitors and neuroprotective agents have been shown to be more efficacious in the prevention and treatment of Alzheimer’s disease. Therefore, the purpose of this work was to assess the neuroprotective impact of the combination of quercetin, a major polyphenolic compound, and donepezil, a cholinesterase inhibitor, against hydrogen peroxide-induced oxidative damage of glioblastoma (U-118 MG) cells. Following pretreatment with quercetin and donepezil, the glioblastoma cell line was subjected to H2O2-induced oxidative stress damage via application of 250 μMH2O2 and incubation for a period of 24 h. In this study, four test groups were selected for the investigation of quercetin and donepezil as protective agents against H2O2 oxidative stress. First, quercetin and donepezil were examined in terms of their effects on glioblastoma cell viability. Next, pre- and post-application of quercetin and donepezil were used to determine their concentrations effective against the H2O2-induced oxidative damage in the U-118 MG cell line. Finally, the effect of the combined application of quercetin and donepezil on the cell viability was investigated. Viability testing of the cell lines was carried out via the advanced XTT assay using sulfonated tetrazolium. As a result of testing, no protective or therapeutic effects of donepezil alone were observed on the cell damage caused by oxidative stress. On the other hand, quercetin and combination applications exhibited protective or therapeutic effects on the cell damage. Thus, the neuroprotective effect of quercetin and its combination with donepezil provide a new approach to the search for drugs in the clinical treatment of neurodegenerative diseases.
Similar content being viewed by others
References
J. A. Ross, C. M. Kasum, Anu. Rev. Nutr., 22, 19 – 34 (2002).
N. Rishitha and A. Muthuraman, Life Sci., 199, 80 – 87 (2018).
X. Li, H. Wang, Y. Gao, et al., Am. J. Transl. Res., 8, 3554 – 3558 (2016).
H. E. El-Horany, R. N. A. El-latif, M. M. Elbatsh, et al., J. Biochem. Mol. Toxicol., 30(7), 360 – 369 (2016).
R. Sandhir and A. Mehrotra, Biochim. Biophys. Acta., 1832(3), 421 – 430 (2013).
S. Alok, S. K. Jain, A. Verma, et al., Asian Pac. J. Trop. Biomed., 1(78), 84 (2014).
I. Jantan,W. Ahmad, S. N. A. Bukhari, Front. Recent Dev. Plant Sci., 6, 655 (2015).
H. Khan, H. Ullah, M. Aschner, et al., Biomolecules, 10(1), 59 (2020).
S. L. Rogers and L. T. Friedhoff, Dementia Geriatr. Cognit. Disord., 7(6), 293 – 303 (1996).
E. I. Solntseva, N. A. Kapai, O. V. Popova, et al., Brain Res. Bull., 106, 56 – 61 (2014).
M. Zimmermann, Br. J. Pharmacol., 170(5), 953 – 967(2013).
Y. Yoshiyama, A. Kojima, C. Ishikawa, et al., J. Alzheimer’s Dis., 22(1), 295 – 306 (2010).
C. Loy and L. Schneider, Cochrane Database of Systematic Reviews, (2006), Issue 1.
J. P. Rowland, J. Rigby, A. C. Harper, et al., Adv. Psychiatr. Treat., 13(3), 178 – 184 (2007).
K. S. Gugnani, N. Vu, A. N. Rondón-Ortiz, et al., Toxicol. Appl. Pharmacol., 340, 67 – 76 (2018).
D. Jantas, J. Malarz, T. N. Le, and A. Stojakowska., Int. J. Mol. Sci., 22(19), 10363 (2021).
A. González-Sarrías, M. A. Núñez-Sánchez, F. A. Tomás-Barberán, and J. C. Espín, J. Agric. Food Chem., 65(4), 752 – 758 (2017).
D. Pamies, A. Bal-Price, A. Simeonov, et al., ALTEX, 34(1), 95 – 132 (2017).
E. Dinc, L. Ayaz, and A. H. Kurt, Curr. Eye Res., 42(12), 1659 – 1666 (2017).
T. L. Riss, R. A. Moravec, A. L Niles, et al., Assay Guidance Manual [Internet 2016].
L. G. Costa, J. M. Garrick, P. J. Roquè, et al., Oxid. Med. Cell. Longevity, 2016.
H. Dong, C. M. Yuede, C. A. Coughlan, et al., Brain Res., 1303,169 – 178 (2009).
A. M. Sabogal-Guáqueta, J. I. Munoz-Manco, J. R. Ramírez-Pineda, et al., Neuropharmacoogy., 93, 134 – 145 (2015).
B. Ossola, T. M. Kääriäinen, and P. T. Männistö, Expert Opin. Drug Saf., 8(4), 397 – 409 (2009).
M. A. Ansari, H. M. Abdul, G. Joshi, et al., J. Nutr. Biochem., 20(4), 269 – 275(2009).
J. Jakubowicz-Gil, W. Rzeski, B. Zdzisinska, et al., Acta Neurobiol. Exp., 68(2), 139 (2008).
H. J. Heo and C. Y. Lee, J. Agric. Food Chem., 52(25), 7514 – 7517 (2004).
N. Sasaki, T. Toda, T. Kaneko, et al., Chem. Biol. Interact., 145 (1), 101 – 116 (2003).
A. C. Silveira, J. P. Dias, V. M. Santos, et al., Curr. Neuropharmacol., 17(7), 590 – 613 (2019).
S. H. Kim, N. Kandiah, J. L. Hsu, et al., Br. J. Pharmacol., 17(23), 4224 – 4232 (2017).
A. C. Baakman, R. Alvarez-Jimenez, G. Loewen, et al., Transl. Res. Clin. Interventions, 5, 89 – 98 (2019).
M. Racchi, M. Mazzucchelli, E. Porrello, et al., Pharmacol. Res., 50(4), 441 – 451 (2004).
E. Arias, S. Gallego-Sandín, M. Villarroya, et al., J. Pharmacol. Exp. Ther., 315(3), 1346 – 1353 (2005).
Y. Takada-Takatori, T. Kume, Y. Izumi, et al., Biol. Pharm. Bull., 32(3), 318 – 324 (2009).
M. Kimura, S. Akasofu, H. Ogura, et al., Brain Res., 1047(1), 72 – 84 (2005).
J. Meunier, J. Ieni, and T. Maurice, Br. J. Pharmacol, 149(8), 998 – 1012 (2006).
M. Y. Noh, S. H. Koh, S. M. Kim, et al., J. Neurochem., 127(4), 562 – 574 (2013).
M. Y. Noh, S. H. Koh, Y. Kim, et al., J. Neurochem., 108(5), 1116 – 1125 (2009).
A. Akaike, Alzheimer Dis. Assoc. Disord., 20, S8-S11 (2006).
Y. Takada, A. Yonezawa, T. Kume, et al., J. Pharmacol. Exp. Ther., 3(2), 772 – 777 (2003).
H. Shen, T. Kihara, H. Hongo, et al., Br. J. Pharmacol., 61 (1), 127 – 139 (2010).
S. Akasofu, M. Kimura, T. Kosasa, et al., Chem.-Biol. Interact., 17(1 – 3), 222 – 226 (2008).
S. Haider, S. Saleem, T. Perveen, et al., Age, 36(3), 1291 – 1302 (2014).
X. Yu, Y. Li, and X. Mu, BioMed Res. Int., 2020.
R. Rezaei-Sadabady, A. Eidi, N. Zarghami, et al., Artif. Cells, Nanomed., Biotechnol., 44(1), 128 – 134 (2016).
F. Arredondo, C. Echeverry, J. A. Abin-Carriquiry, et al., Free Radical Biol. Med., 49(5), 738 – 747 (2010).
S. Singh, S. K. Singh, M. Kumar, et al., Toxicol. Int., 18(2), 140 (2011).
Funding
The Kahramanmaraş Sutcu Imam University supported this work (Project No: 2019/4 – 22D). We would also like to thank Ali Raif İlaç Sanayi (ARIS) for their support by supplying the donepezil hydrochloride.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Ahmet, A., Hakan, K.A., Derya, K. et al. Protective Effects of Quercetin in Combination with Donepezil against H2O2-Induced Oxidative Stress in Glioblastoma Cells. Pharm Chem J 56, 1577–1586 (2023). https://doi.org/10.1007/s11094-023-02830-3
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11094-023-02830-3