Trapping Methylglyoxal by Taxifolin and Its Metabolites in Mice

Abstract

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.