Scavenging Glyoxal and Methylglyoxal by Synephrine and Neohesperidin from Flowers of Citrus aurantium L. var. amara Engl. in Mice and Humans

There is considerable research evidence that alpha-dicarbonyl compounds, including glyoxal (GO) and methylglyoxal (MGO), are closely related to many chronic diseases. In this work, after comparison of the capture capacity, reaction pathway, and reaction rate of synephrine (SYN) and neohesperidin (NEO) on GO/MGO in vitro, experimental mice were administrated with SYN and NEO alone and in combination. Quantitative data from UHPLC-QQQ-MS/MS revealed that SYN/NEO/HES (hesperetin, the metabolite of NEO) could form the GO/MGO-adducts in mice (except SYN-MGO), and the levels of GO/MGO-adducts in mouse urine and fecal samples were dose-dependent. Moreover, SYN and NEO had a synergistic scavenging effect on GO in vivo by promoting each other to form more GO adducts, while SYN could promote NEO to form more MGO-adducts, although it could not form MGO-adducts. Additionally, human experiments showed that the GO/MGO-adducts of SYN/NEO/HES found in mice were also detected in human urine and fecal samples after drinking flowers of Citrus aurantium L. var. amara Engl. (FCAVA) tea using UHPLC-QTOF-MS/MS. These findings provide a novel strategy to reduce endogenous GO/MGO via the consumption of dietary FCAVA rich in SYN and NEO.