Rutin Attenuates Cuprizone-Induced Demyelination in C57bl/6 Mice Through Activation of Nrf2 Signaling and Inhibition of Nf-Κb Publisher

Summary: Could a new compound protect nerves in MS? Preclinical experiments suggest anti-inflammatory and antioxidant activity, but human effectiveness remains unknown. #MultipleSclerosis #Neuroinflammation

Alavi S D ; Shirooie S ; Sureda A ; Farzaei M H ; Fakhri S ; Asgary S
Source: Iranian Journal of Basic Medical Sciences Published:2026

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 anti-oxidant defenses and inhibiting neuroinflammation, highlighting it as a promising candidate for further studies on demyelinating disorders such as MS. © 2026. This work is openly licensed via CC BY 4.0. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.