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

Abstract

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.

American Ginseng for the Treatment of Alzheimer’s Disease: A Review

“…Therefore, we speculate that AG polysaccharides may ameliorate AD symptoms. Moreover, flavonoids can be divided into flavonoids, flavanones, isoflavones, flavonols, etc., which can play an anti-AD role by inhibiting Aβ production and aggregation, as well as displaying antiinflammatory, anti-oxidant, anti-bacterial and anti-viral properties [238]. Therefore, we believe that the flavonoid components in AG have research value for their potential use in anti-AD treatments.…”

Extracts of Sideritis scardica and Clinopodium vulgare Alleviate Cognitive Impairments in Scopolamine-Induced Rat Dementia

“…Phenols (ArOH), a diverse group of metabolites originating from the secondary metabolism of plants, possess the outstanding property of suppressing or delaying the spontaneous autoxidation of organic molecules [83,84]. Polyphenols, particularly flavonoids, can traverse the blood-brain barrier, rendering them suitable as anti-AD natural agents [85]. The reported anti-amyloidogenic features, AChE inhibitory activity and cognitive declinepreventing effects of polyphenols and flavonoids [85][86][87] underscore their potential therapeutic relevance.…”

“…Polyphenols, particularly flavonoids, can traverse the blood-brain barrier, rendering them suitable as anti-AD natural agents [85]. The reported anti-amyloidogenic features, AChE inhibitory activity and cognitive declinepreventing effects of polyphenols and flavonoids [85][86][87] underscore their potential therapeutic relevance.…”

Anti-Alzheimer Activity and UHPLC-MS Based Molecular Networking of Pseudobombax ellipticum Cultivars Coupled to Multivariate Data Analysis and In Silico Molecular Docking.

“…This work is considered as a step towards investigating the anti-Alzheimer activity of the tested extracts. Although compared to Donepezil (positive standard), the tested extracts didn't show significant anticholinesterase activity, some of the identified metabolites had previously reported anticholinesterase activity [36][37] [38]. This drove the author's interest to perform docking studies on these compounds to explore this activity at the molecular level.…”