Effects of Nobiletin in Animal Models of Cognitive Impairment: Current Insights and Future Perspectives

Alzheimer's disease (AD) is characterized by the progressive decline of cognitive function and has a devastating impact on the whole of society. Despite intensive laboratory and clinical research, no pharmacological options are currently available for the prevention and effective long-term treatment of AD. Nobiletin, a polymethoxylated flavone from the peel of Citrus depressa, has been demonstrated to exhibit memory-improving effects in various animal models of AD, including a triple transgenic mouse model (3XTg-AD). Furthermore, it exerts a wide range of beneficial effects against pathological features of AD, including amyloid beta (Aβ) pathology, hyperphosphorylation of tau, oxidative stress, cholinergic neurodegeneration, and dysfunction of synaptic plasticity-related signaling. These results suggest that this natural compound has the potential to become a novel drug for the treatment and prevention of AD.