title: Genistein inhibits advanced glycation end product formation by trapping methylglyoxal.
abstract: Methylglyoxal (MGO) is a highly reactive endogenous metabolite derived from several nonenzymatic and enzymatic reactions, and identified as a well-known precursor of advanced glycation end products (AGEs). In the present study, genistein, a naturally occurring isoflavone derived from soy products, demonstrated significant trapping effects of MGO and consequently formed mono- and di-MGO adducts under physiological conditions (pH 7.4, 37 °C). More than 80.0% of MGO was trapped within 4 h, and the trapping efficiency could be up to 97.7% at 24 h. The reaction adducts formed from genistein and MGO under different ratios were analyzed using LC/MS. We also successfully purified and identified the major mono- and di-MGO conjugated adducts of genistein. The NMR data showed that positions 6 and 8 of the A ring of genistein were the major active sites for trapping MGO. We further demonstrated that genistein could effectively inhibit the formation of AGEs in the human serum albumin (HSA)-MGO assay. Two mono-MGO adducts and one di-MGO adduct of genistein were detected in this assay using LC/MS. The di-MGO adduct of genistein became the dominant reaction product during prolonged incubation. Results from this study, as well as our previous findings on (-)-epigallocatechin 3-gallate (EGCG), phloridzin and phloretin, indicate that dietary flavonoids that have the same A ring structure as genistein, EGCG, phloridzin, and phloretin may have the potential to inhibit the formation of AGEs by trapping reactive dicarbonyl species.
authors.affiliation: Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC 28081, United States.
authors.forename: Lishuang
authors.initials: L
authors.lastname: Lv
authors.forename: Xi
authors.initials: X
authors.lastname: Shao
authors.forename: Huadong
authors.initials: H
authors.lastname: Chen
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.forename: Shengmin
authors.initials: S
authors.lastname: Sang
mesh_terms: D002851:Chromatography, High Pressure Liquid; D019833:Genistein / Q000737:chemistry*; D017127:Glycation End Products, Advanced / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011765:Pyruvaldehyde / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry; D013696:Temperature; D013997:Time Factors
chemical_list: D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D011765:Pyruvaldehyde; D019833:Genistein