Journal of Isfahan Medical School

Journal of Isfahan Medical School

Investigation of the Effects of Fisetin in the Prevention of Oligodendrocyte Cell Death and Serum Level of TGF-Β in a Toxic Model of Brain Myelin Destruction in Mice Introduction

Document Type : Original Article(s)

Authors
Armina Bahador 1
Ebrahim Esfandiari 2
Nazem Ghasemi 3
1 MSc Student, Department of Anatomical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
2 Professor, Department of Anatomical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
3 Associate Professor, Department of Anatomical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
10.48305/jims.v43.i843.1728
Abstract
Background: The most important therapeutic goals for improving the condition of patients with neurodegenerative diseases are to prevent neuronal cell death and replace damaged cells with cell transplantation. Recently, the use of flavonoids has attracted the attention of researchers due to their anti-inflammatory and neuroprotective effects and with the aim of preventing cell death and promoting cell differentiation. In the present study, the effects of fisetin as a flavonoid were investigated on the prevention of oligodendrocyte death and serum levels of TGF-β in a toxic model of brain myelin destruction.
Methods: C57BL/6 mice were divided into control, sham, cuprizone, fisetin, and cuprizone-fisetin groups. Oligodendrocyte death was induced using cuprizone. Additionally, fisetin was used at a dose of 20 mg/kg in the treated groups. Finally, immunohistochemical staining was used to examine oligodendrocyte markers and ELISA was used to assess serum levels of TGF-β. The results were evaluated and compared using One Way ANOVA.
Findings: The mean serum levels of TGF-β and the mean percentage of MOG and Olig2 positive cells in the fisetin-treated groups were significantly increased compared to the cuprizone group (P ≤ 0.05, P ≤ 0.05 and P ≤ 0.01, respectively).
Conclusion: Oligodendrocyte cell death caused by exposure to toxic agents such as cuprizone can be suppressed by flavonoids such as fisetin. Fisetin can maintain the oligodendrocyte population and prevent the development of neurodegenerative diseases by exerting anti-inflammatory and neuroprotective effects.

Highlights

Armina Bahador: Google Scholar , PubMed

Ebrahim Esfandiari: Google Scholar , PubMed

Nazem Ghasemi: Google Scholar , PubMed

Keywords
Fisetin
Oligodendroglia
Transforming growth factor beta

Subjects

1.     Lotfi MS, Kalalinia F. Flavonoids in Combination with stem cells for the treatment of neurological disorders. Neurochemical Research 2023; 48(11): 3270-82.
2.     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): 101-108.
3.     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.
4.     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): 1617-1625
5.     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):34.
6.     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.
7.     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.
8.     Yousefzadeh MJ, Zhu Y, 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.
9.     Blagosklonny MV. Anti-aging: senolytics or gerostatics (unconventional view). Oncotarget 2021; 12(18): 1821-35.
10.  Hassan SSU, Samanta S, Dash R, Karpiński TM, Habibi E, Sadiq A, Ahmadi A, Bunagu S. The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress. Front Pharmacol  2022; 13: 1015835.
11.  Hiew LF, Poon CH, You HZ, Lim LW. TGF-β/Smad signalling in neurogenesis: implications for neuropsychiatric diseases. Cells 2021; 10(6): 1382.
12.  Yoshimura A, Wakabayashi Y, Mori T. Cellular and molecular basis for the regulation of inflammation by TGF-β. The journal of biochemistry 2010; 147(6): 781-92.
13.  Galvez-Contreras A.Y., Zarate-Lopez D., Torres-Chavez A.L., Gonzalez-Perez O. Role of Oligodendrocytes and Myelin in the Pathophysiology of Autism Spectrum Disorder. Brain Sci 2020; 10:951.
14.  Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: pathogenesis, symptoms, diagnoses and cell-based therapy. Cell Journal (Yakhteh) 2016; 19(1): 1.
15.  Tang X, Deng P, Yang H. Neuroprotective Effects of Fisetin by Fighting Neuroinflammation. Frontiers in Medical Science Research 2023; 5 (11).
16.  Chuang JY, Chang PC, Shen YC, Lin C, Tsai CF, Chen JH, Yeh WL, Wu LH, Lin HY, Liu YS, Lu DY. Regulatory effects of fisetin on microglial activation. Molecules 2014; 19(7): 8820-39.
17.  Chen Y, Peng F, Xing Z, Chen J, Peng C, Li D. Beneficial effects of natural flavonoids on neuroinflammation. Frontiers in immunology 2022; 13: 1006434.
18.  Yin X, Liu B, Ding Y, Li X, Sheng J, Guo Y, Chen Z, Wen J. Total flavones of Rhododendron induce the transformation of A1/A2 astrocytes via promoting the release of CBS-produced H2S. Phytomedicine 2023; 111: 154666. 
Journal of Isfahan Medical School
Volume 43, Issue 843
3rd Week, February
January and February 2026
Pages 1728-1734

  • Receive Date 02 November 2025
  • Accept Date 03 May 2026