Trapping Methylglyoxal by Taxifolin and Its Metabolites in Mice.

Trapping of methylglyoxal (MGO), an important precursor of advanced glycation end products (AGEs), is considered an effective therapy for alleviating AGE-induced chronic metabolic diseases. In this paper, taxifolin (Tax) was first found to effectively trap MGO by forming mono- and di-MGO adducts under in vitro conditions. In addition, the mechanism of trapping MGO by Tax was also studied in vivo . Tax was demonstrated to efficiently trap endogenous MGO via formation of mono-MGO adducts in urine and fecal samples of C57BL/6J mice after oral administration of Tax and MGO. Mono-MGO adducts of Tax metabolites, including methylated Tax, aromadendrin, quercetin, and isorhamnetin, were identified in C57BL/6J mice urine and fecal samples by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS). One mono-MGO-Tax was purified from the in vitro reaction mixture, and its structure was elucidated as 6-MGO-Tax based on the analysis of UHPLC-QTOF-MS/MS and detailed nuclear magnetic resonance (NMR) data. Quantification studies demonstrated that Tax and its metabolites trapped MGO in a dose-dependent manner in C57BL/6J mice urine and fecal samples. Furthermore, we also detected mono-MGO adducts of Tax and methylated Tax in urine and fecal samples of diabetic db/db mice after oral administration of Tax. Taken together, our results demonstrated that dietary Tax has the potential to detoxify MGO and treat AGE-associated chronic diseases.