Tea polyphenol (-)-epigallocatechin-3-gallate: a new trapping agent of reactive dicarbonyl species.
Previous studies have demonstrated that reactive dicarbonyl compounds [e.g., methylglyoxal (MGO) and glyoxal (GO)] irreversibly and progressively modify proteins over time and yield advanced glycation end products (AGEs), which are thought to contribute to the development of diabetes mellitus and its subsequent complications. Thus, decreasing the levels of MGO and GO will be an effective approach to reduce the formation of AGEs and the development of diabetic complications. In our studies to find nontoxic trapping agents of reactive dicarbonyl species from dietary sources, we found that (-)-epigallocatechin-3-gallate (EGCG), the major bioactive green tea polyphenol, could efficiently trap reactive dicarbonyl compounds (MGO or GO) to form mono- and di-MGO or GO adducts under physiological conditions (pH 7.4, 37 degrees C). The products formed from EGCG and MGO (or GO), combined at different ratios, were analyzed using LC/MS. We also developed a method to purify the two major mono-MGO adducts of EGCG without derivatization, and their structures were identified as stereoisomers of mono-MGO adducts of EGCG based on their 1D and 2D NMR spectra. Our LC/MS and NMR data showed that positions 6 and 8 of the EGCG A-ring were the major active sites for trapping reactive dicarbonyl compounds. We also found that EGCG lost its trapping efficacy under acidic conditions (pH<or=4), suggesting a base-catalyzed trapping reaction. The purified mono-MGO adducts of EGCG in this study can be used as standards for further in vivo studies on the possible trapping of reactive dicarbonyl species by EGCG.
Sang
Shengmin
S
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, 164 Frelinghuysen Road, Piscataway, New Jersey 08854-8020, USA. ssang@rci.rutgers.edu
Shao
Xi
X
Bai
Naisheng
N
Lo
Chih-Yu
CY
Yang
Chung S
CS
Ho
Chi-Tang
CT
D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification; D017127:Glycation End Products, Advanced / Q000737:chemistry; D006037:Glyoxal / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification; D059808:Polyphenols; D011765:Pyruvaldehyde / Q000737:chemistry*; D013237:Stereoisomerism; D013662:Tea / Q000737:chemistry*
D005419:Flavonoids; D017127:Glycation End Products, Advanced; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D006037:Glyoxal; D011765:Pyruvaldehyde; D002392:Catechin; C045651:epigallocatechin gallate