Protective Effects of Flavonoids against Alzheimer’s Disease: Pathological Hypothesis, Potential Targets, and Structure–Activity Relationship

Alzheimer’s disease (AD) is a neurodegenerative disease with high morbidity and mortality, for which there is no available cure. Currently, it is generally believed that AD is a disease caused by multiple factors, such as amyloid-beta accumulation, tau protein hyperphosphorylation, oxidative stress, and inflammation. Multitarget prevention and treatment strategies for AD are recommended. Interestingly, naturally occurring dietary flavonoids, a class of polyphenols, have been reported to have multiple biological activities and anti-AD effects in several AD models owing to their antioxidative, anti-inflammatory, and anti-amyloidogenic properties. In this review, we summarize and discuss the existing multiple pathogenic factors of AD. Moreover, we further elaborate on the biological activities of natural flavonoids and their potential mode of action and targets in managing AD by presenting a wide range of experimental evidence. The gathered data indicate that flavonoids can be regarded as prophylactics to slow the advancement of AD or avert its onset. Different flavonoids have different activities and varying levels of activity. Further, this review summarizes the structure–activity relationship of flavonoids based on the existing literature and can provide guidance on the design and selection of flavonoids as anti-AD drugs.