Dietary flavonoids: Promising compounds for targeting α-synucleinopathy in Parkinson’s disease

Alpha-synuclein (α-syn) aggregates contribute to neuronal damage and many neurodegenerative disorders (NDs) which are known as α-synucleinopathies. Flavonoids are polyphenolic compounds extensively found in various plant-based food such as fruits and vegetables. They have potential benefits in human health, especially in α-synucleinopathy-associated NDs. This review summarizes the latest scientific evidence on the impact of flavonoids on α-synucleinopathy, particularly in Parkinson’s disease A comprehensive literature search of Web of Science, PubMed, Scopus and Google Scholar was performed to obtain relevant research studies reporting the anti- synucleinopathies effects of dietary flavonoids Baicalein, luteolin, quercetin, myricitrin, epigallocatechin-3-gallate and genistein are among the most effective flavonoids against synucleinopathies. The main mechanisms of action contributing to these effects are reducing α-syn production; preventing α-syn aggregation and reducing preformed aggregates; promoting degradation of intracellular α-syn aggregates through autophagy; modulating the activity/expression of antioxidant enzymes; and protecting dopaminergic neurons from oxidative damage and apoptosis The results of this review highlighted the beneficial effects of flavonoids in the prevention and management of synucleinopathies. However, there is no clinical data that support these effects in humans, which emphasizes the necessity for designing clinical trials to investigate the efficacy, safe dosage, possible side effects and pharmacokinetics characteristics of flavonoids in humans.