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

Objectives: 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.