This study investigated the neuroprotective potential of tomato extract against cuprizone-induced demyelination. Forty-two C57BL/6 male mice were divided into seven groups: control group (standard diet), cuprizone (Cup) group (0.2% cuprizone diet for six weeks), four intervention groups receiving Cup for six weeks followed by varying doses of tomato extract (50 [Cup-T.50 group], 100 [Cup-T.100 group], 200 [Cup-T.200 group], And 400 [Cup-T.400 group] mg/kg body weight) for 21 days, And a group receiving only 400 mg/kg tomato extract [T.400 group] for 21 days. Brain tissue analyses included histopathological evaluation with hematoxylin and eosin staining of cerebral cortex and Luxol fast blue (LFB) staining of the corpus callosum (CC) And spinal cord, plus biochemical assessment of oxidative stress markers. Quantitative NMR spectroscopy revealed 0.08% lycopene in the extract. Histopathological examination showed significant Cup-induced demyelination in the CC and neuronal damage in the cerebral cortex, which were dose-dependently ameliorated by tomato extract. The Cup-T.400 group exhibited significant recovery in myelin content in the CC and reduced neuronal necrosis in the cerebral cortex (p < 0.05). No significant demyelination/remyelination was observed in the LFB-stained spinal cord (p > 0.05). Biochemically, Cup elevated malondialdehyde and protein carbonyl levels while reducing total antioxidant capacity and glutathione levels (p < 0.05). Tomato extract, particularly at 400 mg/kg, significantly mitigated these oxidative stress parameters. These findings suggest that tomato extract exerts neuroprotective effects against cuprizone-induced demyelination through potent antioxidant mechanisms, offering potential therapeutic applications for demyelinating disorders.

Keywords