Scavenging effects of dietary flavonoids on reactive dicaronyl species and their possible implications on the inhibition of the formation of advanced glycation-end products.

摘要

Flavonoids are ubiquitous in nature and many of which occur in fruits, vegetables and beverages. According to chemical structure, flavonoids can be categorized into flavonols, flavones, flavanones, isoflavones, flavanols, anthocyanidins and chalcones. The flavonoids have aroused considerable interest recently because of their potential health benefits. They have been reported to reduce the risk of cancer, cardiovascular diseases, asthma, and diabetes. The objects of this study are to elucidate the structure-activity of dietary flavonoids to trap dicarbonyl species (e.g., glyoxal (GO) and methylglyoxal (MGO)), which are the precursors of advanced glycation end products (AGEs), as well as to study the possible implications on the inhibition of the formation of AGEs by flavonoids. Previous studies have demonstrated that accumulation of reactive dicarbonyl compounds in human tissue will accelerate the vascular damage in both diabetes and uremia. Moreover, advanced glycation progressively and irreversibly modified proteins over time and yielded AGEs. AGEs are thought to contribute to the development of diabetes mellitus and its complications. Higher levels of alpha, beta-dicarbonyl compounds were observed in diabetes patients' plasma than those in healthy people's plasma. Therefore, decreasing the levels of dicarbonyl compounds and consequently inhibiting the formation of AGEs would be a useful approach to prevent the development of diabetic complications.;In this dissertation, we found that polyphenols phloretin and phloridzin from could trap MGO rapidly under in vitro conditions (pH 7.4 buffer solution, 37°C) to form carbonyl adducts of those two compounds. The mono-carbonyl adduct of phloridzin was purified through column chromatography and identified by 1H, 13C, and 2D NMR and MS analysis.;To understand the structure requirements of flavonoids to perform good trapping effects of reactive dicarbonyl compounds, we tested the trapping efficacy of flavonoids with different A-ring, B-ring, and C-ring configuration under in vitro conditions. Genistein, phloretin, and phloridzin were tested under an AGEs condition and all three flavonoids exhibited strong inhibitory effects on the formation AGEs. Two reaction adducts of genistein under such condition were observed using LC/MS, which further confirmed that flavonoids have the ability to prevent the formation of AGEs through trapping of dicarbonyl species.