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Protective Effects of Quercetin in Combination with Donepezil against H2O2-Induced Oxidative Stress in Glioblastoma Cells

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Pharmaceutical Chemistry Journal Aims and scope

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.

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References

  1. J. A. Ross, C. M. Kasum, Anu. Rev. Nutr., 22, 19 – 34 (2002).

    Article  CAS  Google Scholar 

  2. N. Rishitha and A. Muthuraman, Life Sci., 199, 80 – 87 (2018).

    Article  CAS  PubMed  Google Scholar 

  3. X. Li, H. Wang, Y. Gao, et al., Am. J. Transl. Res., 8, 3554 – 3558 (2016).

    Google Scholar 

  4. H. E. El-Horany, R. N. A. El-latif, M. M. Elbatsh, et al., J. Biochem. Mol. Toxicol., 30(7), 360 – 369 (2016).

    Article  CAS  PubMed  Google Scholar 

  5. R. Sandhir and A. Mehrotra, Biochim. Biophys. Acta., 1832(3), 421 – 430 (2013).

    Article  CAS  PubMed  Google Scholar 

  6. S. Alok, S. K. Jain, A. Verma, et al., Asian Pac. J. Trop. Biomed., 1(78), 84 (2014).

    Google Scholar 

  7. I. Jantan,W. Ahmad, S. N. A. Bukhari, Front. Recent Dev. Plant Sci., 6, 655 (2015).

    Google Scholar 

  8. H. Khan, H. Ullah, M. Aschner, et al., Biomolecules, 10(1), 59 (2020).

    Article  CAS  Google Scholar 

  9. S. L. Rogers and L. T. Friedhoff, Dementia Geriatr. Cognit. Disord., 7(6), 293 – 303 (1996).

    Article  CAS  Google Scholar 

  10. E. I. Solntseva, N. A. Kapai, O. V. Popova, et al., Brain Res. Bull., 106, 56 – 61 (2014).

    Article  CAS  PubMed  Google Scholar 

  11. M. Zimmermann, Br. J. Pharmacol., 170(5), 953 – 967(2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Y. Yoshiyama, A. Kojima, C. Ishikawa, et al., J. Alzheimer’s Dis., 22(1), 295 – 306 (2010).

    Article  CAS  Google Scholar 

  13. C. Loy and L. Schneider, Cochrane Database of Systematic Reviews, (2006), Issue 1.

  14. J. P. Rowland, J. Rigby, A. C. Harper, et al., Adv. Psychiatr. Treat., 13(3), 178 – 184 (2007).

    Article  Google Scholar 

  15. K. S. Gugnani, N. Vu, A. N. Rondón-Ortiz, et al., Toxicol. Appl. Pharmacol., 340, 67 – 76 (2018).

    Article  CAS  PubMed  Google Scholar 

  16. D. Jantas, J. Malarz, T. N. Le, and A. Stojakowska., Int. J. Mol. Sci., 22(19), 10363 (2021).

  17. A. González-Sarrías, M. A. Núñez-Sánchez, F. A. Tomás-Barberán, and J. C. Espín, J. Agric. Food Chem., 65(4), 752 – 758 (2017).

    Article  PubMed  Google Scholar 

  18. D. Pamies, A. Bal-Price, A. Simeonov, et al., ALTEX, 34(1), 95 – 132 (2017).

    PubMed  Google Scholar 

  19. E. Dinc, L. Ayaz, and A. H. Kurt, Curr. Eye Res., 42(12), 1659 – 1666 (2017).

    Article  CAS  PubMed  Google Scholar 

  20. T. L. Riss, R. A. Moravec, A. L Niles, et al., Assay Guidance Manual [Internet 2016].

  21. L. G. Costa, J. M. Garrick, P. J. Roquè, et al., Oxid. Med. Cell. Longevity, 2016.

  22. H. Dong, C. M. Yuede, C. A. Coughlan, et al., Brain Res., 1303,169 – 178 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. A. M. Sabogal-Guáqueta, J. I. Munoz-Manco, J. R. Ramírez-Pineda, et al., Neuropharmacoogy., 93, 134 – 145 (2015).

    Article  Google Scholar 

  24. B. Ossola, T. M. Kääriäinen, and P. T. Männistö, Expert Opin. Drug Saf., 8(4), 397 – 409 (2009).

    Article  CAS  PubMed  Google Scholar 

  25. M. A. Ansari, H. M. Abdul, G. Joshi, et al., J. Nutr. Biochem., 20(4), 269 – 275(2009).

    Article  CAS  PubMed  Google Scholar 

  26. J. Jakubowicz-Gil, W. Rzeski, B. Zdzisinska, et al., Acta Neurobiol. Exp., 68(2), 139 (2008).

    Google Scholar 

  27. H. J. Heo and C. Y. Lee, J. Agric. Food Chem., 52(25), 7514 – 7517 (2004).

    Article  CAS  PubMed  Google Scholar 

  28. N. Sasaki, T. Toda, T. Kaneko, et al., Chem. Biol. Interact., 145 (1), 101 – 116 (2003).

    Article  CAS  PubMed  Google Scholar 

  29. A. C. Silveira, J. P. Dias, V. M. Santos, et al., Curr. Neuropharmacol., 17(7), 590 – 613 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. S. H. Kim, N. Kandiah, J. L. Hsu, et al., Br. J. Pharmacol., 17(23), 4224 – 4232 (2017).

    Article  Google Scholar 

  31. A. C. Baakman, R. Alvarez-Jimenez, G. Loewen, et al., Transl. Res. Clin. Interventions, 5, 89 – 98 (2019).

    Article  Google Scholar 

  32. M. Racchi, M. Mazzucchelli, E. Porrello, et al., Pharmacol. Res., 50(4), 441 – 451 (2004).

    Article  CAS  PubMed  Google Scholar 

  33. E. Arias, S. Gallego-Sandín, M. Villarroya, et al., J. Pharmacol. Exp. Ther., 315(3), 1346 – 1353 (2005).

    Article  CAS  PubMed  Google Scholar 

  34. Y. Takada-Takatori, T. Kume, Y. Izumi, et al., Biol. Pharm. Bull., 32(3), 318 – 324 (2009).

    Article  CAS  PubMed  Google Scholar 

  35. M. Kimura, S. Akasofu, H. Ogura, et al., Brain Res., 1047(1), 72 – 84 (2005).

    Article  CAS  PubMed  Google Scholar 

  36. J. Meunier, J. Ieni, and T. Maurice, Br. J. Pharmacol, 149(8), 998 – 1012 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. M. Y. Noh, S. H. Koh, S. M. Kim, et al., J. Neurochem., 127(4), 562 – 574 (2013).

    Article  CAS  PubMed  Google Scholar 

  38. M. Y. Noh, S. H. Koh, Y. Kim, et al., J. Neurochem., 108(5), 1116 – 1125 (2009).

    Article  CAS  PubMed  Google Scholar 

  39. A. Akaike, Alzheimer Dis. Assoc. Disord., 20, S8-S11 (2006).

    Article  CAS  PubMed  Google Scholar 

  40. Y. Takada, A. Yonezawa, T. Kume, et al., J. Pharmacol. Exp. Ther., 3(2), 772 – 777 (2003).

    Article  Google Scholar 

  41. H. Shen, T. Kihara, H. Hongo, et al., Br. J. Pharmacol., 61 (1), 127 – 139 (2010).

    Article  Google Scholar 

  42. S. Akasofu, M. Kimura, T. Kosasa, et al., Chem.-Biol. Interact., 17(1 – 3), 222 – 226 (2008).

    Article  Google Scholar 

  43. S. Haider, S. Saleem, T. Perveen, et al., Age, 36(3), 1291 – 1302 (2014).

    Article  CAS  Google Scholar 

  44. X. Yu, Y. Li, and X. Mu, BioMed Res. Int., 2020.

  45. R. Rezaei-Sadabady, A. Eidi, N. Zarghami, et al., Artif. Cells, Nanomed., Biotechnol., 44(1), 128 – 134 (2016).

  46. F. Arredondo, C. Echeverry, J. A. Abin-Carriquiry, et al., Free Radical Biol. Med., 49(5), 738 – 747 (2010).

    Article  CAS  Google Scholar 

  47. S. Singh, S. K. Singh, M. Kumar, et al., Toxicol. Int., 18(2), 140 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

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.

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Authors and Affiliations

  1. Department of Bioengineering and Sciences, Institute of Natural and Applied Sciences, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey

    Albayrak Ahmet

  2. Department of Pharmacology, Faculty of Medicine, Bolu Abant Izzet Baysal University, Bolu, Turkey

    Kurt Akif Hakan

  3. Afsin Vocational School, Department of Chemistry and Chemical Processing Technologies, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey

    Kilicaslan Derya

  4. Department Medical Genetics, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey

    Celik Mustafa

  5. Department of Interdisciplinary Neuroscience, Bolu Abant Izzet Baysal University, Institute of Health Sciences, Bolu, Turkey

    Oztabag Kara Cansu

  6. Department Biostatistics and Medical Informatics, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey

    Doganer Adem

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  1. Albayrak Ahmet
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  2. Kurt Akif Hakan
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Correspondence to Kurt Akif Hakan.

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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

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