Influence of hydroxyl substitution on the inhibition of flavonoids in advanced glycation end-products formation in glucose-lysine-arginine Maillard reaction models

Advanced glycation end products (AGEs) generated from the Maillard reaction (MR) during food processing in the human physiological environment, have been proven to be significantly associated with various chronic metabolic diseases. In this study, 18 flavonoids were investigated to study their effects on AGEs formation during MR within a glucose-lysine-arginine model system. Five AGEs— N ε -carboxymethyl-lysine (CML), N ε -carboxyethyl-lysine (CEL), pyrraline, pentosidine, and argpyrimidine—were determined by high-performance liquid chromatography-mass spectrometry, with inhibitory rates ranging between 0 % and 71.35 %. Isorhamnetin and naringenin exhibited the strongest inhibitory effect on the formation of CML and CEL, respectively, whereas myricetin exhibited the strongest inhibitory effect on pyrraline, pentosidine, and argpyrimidine formation. In addition, each flavonoid was reacted with glyoxal (GO) and methylglyoxal (MGO) to investigate their trapping activities and adducts. The results showed that the 18 flavonoids could effectively clear GO and MGO, with clearance rates of 1.03 %–71.42 % and 0.93 %–69.37 % for GO and MGO, respectively. Six flavonoids—chrysin, naringenin, apigenin, luteolin, diosmetin, and kaempferol—could form adduct products with mono-/di-MGO, with flavonoid to mono-/di-MGO adduct ratios of approximately 6:1, 2:1, 8:1, 23:1, 10:1, and 3:1, respectively. The number and site of phenolic hydroxyl groups, as well as methoxy substitution on the B-ring in flavonoids, had little effect, but phenolic hydroxyl groups at the C-3 position in the C-ring impeded adduct formation. The flavonoids lowered the degradation of glucose itself, and decreased ammonia-induced degradation and Amadori rearrangement product oxidation due to their antioxidant activities, and they trapped the reactive 1,2-di‑carbonyl species via nucleophilic addition reaction to form AGEs.