Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Berberine protects against behavioral deficits, memory dysfunction, and callosal demyelination in cuprizone-intoxicated C57BL/6 mice

Articles in Press

Document Type : Original Article

Authors
Mohaddeseh Sadat Alavi 1, 2
Seyede Faeze Hosseini 3
Amir Afkhami-Goli 3
Mahsa Aminizade 2
Emad Mokarramdust 2
Naghmeh Layegh Khavidaki 4
Fatemeh Forouzanfar 5
Hamid Reza Sadeghnia 1, 2
1 Pharmacological Research Center of Medicinal Plants, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
2 Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3 Department of Basic Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
4 Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
5 Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
10.22038/ijbms.2026.95172.20524
Abstract
Objective(s): Multiple sclerosis (MS) is a neurological disorder marked by progressive demyelination and neuroinflammation. Berberine, a plant-derived isoquinoline alkaloid found in Berberis species, has notable anti-inflammatory and antioxidant properties. This study aimed to evaluate berberine’s protective effects against cuprizone intoxication in C57BL/6 mice.
Materials and Methods: C57BL/6 mice received a cuprizone-containing diet (0.2% w/w) for five weeks and were concurrently treated with berberine (5 or 10 mg/kg). Body weight, motor coordination, exploratory and locomotor activity, memory function, oxidative stress biomarkers, and inflammatory cytokines were assessed. Histopathological evaluation of myelination was performed using Luxol Fast Blue staining.
Results: Berberine treatment improved exploratory behavior, locomotor activity, and memory function compared with cuprizone-only mice. Oxidative stress analysis showed that berberine significantly reduced malondialdehyde (MDA) levels and increased total thiol content. Berberine also attenuated cuprizone-induced increases in interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Histological findings indicated that berberine preserved myelin integrity, prevented myelin degradation, and reduced the severity of demyelination in the corpus callosum.
Conclusion: These findings indicate that berberine confers protective effects against cuprizone-induced behavioral deficits, memory dysfunction, and callosal demyelination in C57BL/6 mice. The neuroprotective actions of berberine appear to be mediated by suppression of oxidative stress and inflammatory cytokines.
Keywords
Berberine
Cuprizone
Demyelination
Multiple sclerosis
Oxidative stress
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 19 July 2026