Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Rutin attenuates cuprizone-induced demyelination in C57BL/6 mice through activation of Nrf2 signaling and inhibition of NF-κB

Articles in Press

Document Type : Original Article

Authors
Seyede Darya Alavi 1
Samira Shirooie 2
Antoni Sureda 3, 4
Mohammad Hosein Farzaei 2
Sajad Fakhri 2
1 Student Research Committee, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
2 Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
3 Research Group on Community Nutrition and Oxidative Stress (NUCOX) and Health Research Institute of Balearic Islands (IdISBa), University of Balearic Islands-IUNICS, Palma de MallorcaE-07122, Balearic Islands, Spain
4 CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
10.22038/ijbms.2026.93649.20195
Abstract
Objective(s): Multiple sclerosis (MS) is a debilitating demyelinating disease characterized by oxidative stress and neuroinflammation. This study investigated the therapeutic potential of rutin, a natural flavonoid, in a cuprizone (CPZ)-induced mouse model of demyelination.
Materials and Methods: Male C57BL/6 mice were fed a 0.2% CPZ diet for six weeks to induce central nervous system demyelination and were concurrently treated with rutin (50 or 100 mg/kg, intraperitoneally, for the last 14 days). Behavioral assessments, histochemical examinations, and immunohistochemistry for Nrf2, HO-1, NQO-1, and NF-kB p65 were then performed.
Results: Behavioral tests revealed that rutin dose-dependently improved CPZ-induced motor coordination deficits in the pole, rotarod, and open-field tests. Histological analysis (LFB and H&E staining) demonstrated that rutin significantly attenuated demyelination in the corpus callosum. Mechanistically, immunohistochemistry showed that rutin treatment effectively up-regulated the key antioxidant pathway by increasing the expression of phosphorylated Nrf2 (p-Nrf2) and its downstream targets (HO-1 and NQO-1), while simultaneously suppressing the pro-inflammatory NF-κB p65 pathway.
Conclusion: Our findings show that rutin protects against demyelination through a dual mechanism of enhancing endogenous antioxidant defenses and inhibiting neuroinflammation, highlighting it as a promising candidate for further studies on demyelinating disorders such as MS.
Keywords
Cuprizone
Demyelination
Mice
NF-kB
Nrf2
Rutin
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 26 September 2026