Apple polyphenols, phloretin and phloridzin: new trapping agents of reactive dicarbonyl species.
Reactive dicarbonyl species, such as methylglyoxal (MGO) and glyoxal (GO), have received extensive attention recently due to their high reactivity and ability to form advanced glycation end products (AGEs) with biological substances such as proteins, phospholipids, and DNA. In the present study, we found that both phloretin and its glucoside, phloridzin, the major bioactive apple polyphenols, could efficiently trap reactive MGO or GO to form mono- and di-MGO or GO adducts under physiological conditions (pH 7.4, 37 degrees C). More than 80% MGO was trapped within 10 min, and 68% GO was trapped within 24 h by phloretin. Phloridzin also had strong trapping efficiency by quenching more than 70% MGO and 60% GO within 24 h. The glucosylation of the hydroxyl group at position 2 could significantly slow down the trapping rate and the formation of MGO or GO adducts. The products formed from phloretin (or phloridzin) and MGO (or GO), combined at different ratios, were analyzed using LC/MS. We successfully purified the major mono-MGO adduct of phloridzin and found that it was a mixture of tautomers based on the one- and two-dimensional NMR spectra. Our LC/MS and NMR data showed that positions 3 and 5 of the phloretin or phloridzin A ring were the major active sites for trapping reactive dicarbonyl species. We also found that phloretin was more reactive than lysine and arginine in terms of trapping reactive dicarbonyl species, MGO or GO. Our results suggest that dietary flavonoids that have the same A ring structure as phloretin may have the potential to trap reactive dicarbonyl species and therefore inhibit the formation of AGEs.
Shao
Xi
X
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, 164 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
Bai
Naisheng
N
He
Kan
K
Ho
Chi-Tang
CT
Yang
Chung S
CS
Sang
Shengmin
S
D002853:Chromatography, Liquid; D005419:Flavonoids / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry / Q000302:isolation & purification; D009682:Magnetic Resonance Spectroscopy; D027845:Malus / Q000737:chemistry*; D013058:Mass Spectrometry; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry*; D010693:Phloretin / Q000737:chemistry*; D010695:Phlorhizin / Q000737:chemistry*; D059808:Polyphenols
D005419:Flavonoids; D005609:Free Radicals; D010636:Phenols; D059808:Polyphenols; D010695:Phlorhizin; D010693:Phloretin