Investigation of the Protective and Anti-Inflammatory Effects of Fisetin on Serum Levels of Interferon- Gamma and Myelin Basic Protein Expressing Cells Survival in the Mouse Brain Following Cuprisone Gavage

Document Type : Original Article(s)

Authors

1 MSc Student, Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Professor, Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Associate Professor, Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: External toxic agents with nuclear antigens similar to myelin basic proteins can activate immune cells and destroy the myelin sheath. Fisetin is vital in preventing nerve damage because of its neuroprotective effects. In the present study, the effects of fisetin were investigated on the interferon-gamma (IFN-Ɣ) serum levels and prevention of Mbp-expressing cell death in the mouse brain.
Methods: 20 C57BL/6 mice were divided into five groups: control, sham, cuprizone, fisetin, and cuprizone/fisetin. Cuprizone was used to induce the death of MBP-positive cells. At the end of the study, the serum level of Interferon-gamma was determined by ELISA, and the average percentage of Mbp-positive cells was determined by immunohistochemistry technique. Finally, the data were analyzed using the One-Way ANOVA test
Findings: The mean expression of the inflammatory factor Interferon-gamma in the fisetin-receiving group was significantly reduced compared to the cuprizone group (P ≤ 0.001). Also, following the use of cuprizone, the mean percentage of Mbp-positive cells in the cuprizone group was significantly reduced compared to the other groups (P ≤ 0.05).
Conclusion: Cuprizone can increase the death of neuroglial cells expressing the Mbp factor by raising serum levels of the inflammatory factor Interferon-gamma. The results of this study indicate that fisetin, as a type of flavonoid, can play a crucial role in protecting neuroglial cells by exerting anti-inflammatory and neuroprotective effects and reducing the destructive effects of inflammatory factors on nervous tissue.

Highlights

Armina Bahador: PubMed ,Google Scholar

Ebrahim Esfandiari: PubMed ,Google Scholar

Nazem Ghasemi: PubMed ,Google Scholar

Keywords

Main Subjects

References

  1. Zirngibl M, Assinck P, Sizov A, Caprariello AV, Plemel JR. Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination. Mol Neurodegener 2022; 17(1):
  2. Avşar T, Erdem GC, Terzioğlu G, Turanli ET. Investigation of neuro-inflammatory parameters in a cuprizone induced mouse model of multiple sclerosis. Turk J Biol 2021; 45(5): 644-55.
  3. Razavi S, Nazem G, Mardani M, Esfandiari E, Salehi H, Zarkesh Esfahani SH. Neurotrophic factors and their effects in the treatment of multiple sclerosis. Adv Biomed Res 2015; 4:
  4. Imran M, Saeed F, Gilani SA, Shariati MA, Imran A, Afzaal M, et al. Fisetin: An anticancer perspective. Food Sci Nutr 2021; 9(1): 3-16.
  5. Elsallabi O, Patruno A, Pesce M, Cataldi A, Carradori S, Gallorini M. Fisetin as a senotherapeutic agent: biopharmaceutical properties and crosstalk between cell senescence and neuroprotection. Molecules 2022; 27(3): 738.
  6. Zhang S, Xue R, Geng Y, Wang H, Li W. Fisetin prevents HT22 cells from high glucose-induced neurotoxicity via PI3K/Akt/CREB signaling pathway. Front Neurosci 2020; 14: 241.
  7. Yousefzadeh MJ, Zhu YI, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine 2018; 36: 18-28.
  8. Blagosklonny MV. Anti-aging: Senolytics or gerostatics (unconventional view). Oncotarget 2021; 12(18): 1821-35.
  9. Hassan SS, Samanta S, Dash R, Karpiński TM, Habibi E, Sadiq A, et al. The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress. Front Pharmacol 2022; 13:
  10. Ghosouri S, Soleimani M, Bakhtiari M, Ghasemi N. Evaluation of in vivo lithium chloride effects as a GSK3-β inhibitor on human adipose derived stem cells differentiation into oligodendrocytes and re-myelination in an animal model of multiple sclerosis. Mol Biol Rep 2023; 50(2): 1617-25.
  11. Ghosouri S, Bakhtiari M, Mitra S, Ghasemi N. Valproic acid effects on human adipose-derived stem cell differentiation into oligodendrocytes and improved remyelination in a mouse model of Multiple Sclerosis. Int J Dev Biol 2023; 67(3): 101-8.
  12. Bakhtiari M, Ghasemi N, Salehi H, Amirpour N, Kazemi M, Mardani M. Evaluation of Edaravone effects on the differentiation of human adipose derived stem cells into oligodendrocyte cells in multiple sclerosis disease in rats. Life Sci 2021; 282: 119812.
  13. Mardani M, Ganji R, Ghasemi N, Kazemi M, Razavi S. Impact of intraventricular human adipose-derived stem cells transplantation with pregnenolone treatment on remyelination of corpus callosum in a rat model of multiple sclerosis. Cell J 2022; 24(12): 748-56.
  14. Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: pathogenesis, symptoms, diagnoses and cell-based therapy. Cell J 2017; 19(1):1-10.
  15. Gao X, Gillig TA, Ye P, D'Ercole AJ, Matsushima GK, Popko B. Interferon-γ protects against cuprizone-induced demyelination. Mol Cell Neurosci 2000; 16(4): 338-49.
  16. Jiang Y, Tang X, Deng P, Jiang C, He Y, Hao D, et al. The Neuroprotective Role of Fisetin in Different Neurological Diseases: A Systematic Review. Mol Neurobiol 2023; 60(11): 6383-94.
  17. Rauf A, Abu-Izneid T, Imran M, Hemeg HA, Bashir K, Aljohani AS, et al. Therapeutic potential and molecular mechanisms of the multitargeted flavonoid fisetin. Curr Top Med Chem 2023; 23(21): 2075-96.
  18. Zhou C, Huang Y, Nie S, Zhou S, Gao X, Chen G. Biological effects and mechanisms of fisetin in cancer: a promising anti-cancer agent. Eur J Med Res 2023; 28(1): 297.
  19. Prem PN, Sivakumar B, Boovarahan SR, Kurian GA. Recent advances in potential of Fisetin in the management of myocardial ischemia-reperfusion injury–A systematic review. Phytomedicine 2022; 101: 154123.
  20. Qnais E, Alqudah A, Bseiso Y, Gammoh O, Wedyan M, Alotaibi B. Exploring the therapeutic potential of fisetin: a comprehensive study on its anti-nociceptive and anti-inflammatory effects. Eur Rev Med Pharmacol Sci 2023; 27(21): 10773-84.
  21. Pal HC, Pearlman RL, Afaq F. Fisetin and its role in chronic diseases. Adv Exp Med Biol 2016; 928: 213-44.
  22. Digehsara SG, Name N, Sartipnia N, Karim E, Taheri S, Ebrahimi MT, et al. Analysis of inflammasomes and CYP27B1 genes in cuprizone demyelinated C57BL/6 mice and evaluation of Th1 and Th2 patterns after oral administration of Lactobacillus casei strain T2 (IBRC-M10783). Microb Pathog 2021; 155: 104931.
  23. Sun Y, Qin H, Zhang H, Feng X, Yang L, Hou DX, et al. Fisetin inhibits inflammation and induces autophagy by mediating PI3K/AKT/mTOR signaling in LPS-induced RAW264. 7 cells. Food Nutr Res 2021; 65.
  24. Gelderblom M, Leypoldt F, Lewerenz J, Birkenmayer G, Orozco D, Ludewig P, et al. The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle artery occlusion in mice. J Cereb Blood Flow Metab 2012; 32(5): 835-43.
  25. Kim SC, Kang SH, Jeong SJ, Kim SH, Ko HS, Kim SH. Inhibition of c-Jun N-terminal kinase and nuclear factor κ B pathways mediates fisetin-exerted anti-inflammatory activity in lipopolysccharide-treated RAW264. 7 cells. Immunopharmacol Immunotoxicol 2012; 34(4): 645-50.
  26. Khatoon S, Samim M, Dahalia M. Fisetin provides neuroprotection in pentylenetetrazole-induced cognition impairment by upregulating CREB/BDNF. Eur J Pharmacol 2023; 944:
Journal of Isfahan Medical School
Volume 43, Issue 802
2nd Week, April
March and April 2025
Pages 46-52

Files

History

  • Receive Date: 14 December 2024
  • Accept Date: 16 February 2025

Share

How to cite

Statistics