Synephrine Synergistically Enhances the Capture of 4-Hydroxynonenal in Mice by Cyanidin-3-O-glucoside

4-Hydroxynonenal (4-HNE), a highly reactive α,β-unsaturated aldehyde, is involved in the pathogenesis of several chronic diseases. In this study, we investigated the kinetics of 4-HNE with cyanidin-3-O-glucoside (C3G) and elucidated the pathways of C3G-4-HNE adduct formation using UHPLC-MS/MS. SYN was identified as an enhancer that improves the 4-HNE clearance rate and promotes adduct formation. When combined with SYN, the clearance rate of 5 mM C3G (3/2 mM) reached 90% within 8 h (12 h/24 h), compared to less than 60% for C3G alone within 24 h. UHPLC-MS/MS analysis revealed that C3G and its metabolite, phloroglucinol aldehyde (PGA), form 4-HNE adducts in a dose-dependent manner in mouse feces. Compared to the use of C3G alone (200/400 mg/kg bw), the combination with SYN (40/80 mg/kg bw) significantly enhanced the formation of 4-HNE adducts, increasing it by 7.19-8.27-fold. This synergy suggests a novel strategy for enhancing 4-HNE clearance in vivo.