Fig. 2.

Beneficial activities of nobiletin in senescence-accelerated mouse prone 8 (SAMP8). In SAMP8 mice, abnormal gene expression may induce mitochondrial dysfunction and oxidative stress with age. Furthermore, tau hyperphosphorylation may lead to deficits in the formation of dendritic spines and neural networks, resulting in cognitive impairment in SAMP8. Treatment with nobiletin significantly decreased protein carbonyl levels, an index of protein oxidation and tau phosphorylation in the brain of SAMP8 mice, which was associated with the restoration of decreased GSH/GSSG ratio as well as increased glutathione peroxidase (GPx) activity. These results suggest nobiletin improves cognitive impairment in SAMP8 mice, at least in part, by reducing oxidative stress and tau hyperphosphorylation.