The multifunctional roles of flavonoids against the formation of advanced glycation end products (AGEs) and AGEs-induced harmful effects

Advanced glycation end products (AGEs) play a crucial role in the onset, progression, and propagation of both macroangiopathy and microangiopathy complications associated with diabetes mellitus, while some dietary flavonoids and their derivatives were proved to be potential in the controlling of AGEs during the past decades. In this review, the multifunctional effects of flavonoids were summarized in the aspect of inhibiting the formation of AGEs and attenuating AGEs-induced harmful effects. A multitude of plant-derived flavonoids have been examined of their antiglycative capability in in vitro models, while glycosylation and methylation/methoxylation of flavonoids might decrease the ability of aglycones. Furthermore, the attenuation of AGEs-induced damages by flavonoids were mainly targeted on the receptor of AGEs (RAGE) and through the prevention of MAPKs/NF-κB or TGF-β1 signaling pathway. Besides, during the inhibition of AGEs formation, flavonoids can trap reactive di-carbonyl species (RCS) and form new adducts. Some of these flavonoid-RCS adducts were further proved to possess bioactivities in foods and biological systems.