Natural Polyphenols as Direct Trapping Agents of Lipid Peroxidation-Derived Acrolein and 4-Hydroxy-<italic>trans</italic>-2-nonenal

Acrolein (ACR) and 4-hydroxy-trans-2-nonenal (HNE) are two cytotoxic lipid-derived R, -unsaturated aldehydes which have been implicated as causative agents in the development of carbonyl stress-associated pathologies. In this study, 21 natural polyphenols were screened to identify effective scavenging agents of ACR and/or HNE in simulated physiological conditions. It was found that flavan-3-ols, theaflavins, cyanomaclurin, and dihydrochalcones effectively trapped ACR and HNE by working as sacrificial nucleophiles. The most effective one was phloretin, which quenched up to 99.6% ACR in 90 min and 90.1% HNE in 24 h. Subsequent LC-MS/MS analysis showed that these effective polyphenols formed adducts with ACR and HNE. A major adduct formed from phloretin and ACR was purified, and its structure was characterized by LC-MS and NMR spectroscopy as diACR-conjugated phloretin. The chemical nature of interactions between ACR and polyphenols was proposed as the Michael addition reaction of phloretin to the CdC double bond of ACR, followed by the formation of hemiacetal between the hydroxyl group in the A ring of phloretin and the CdO carbonyl group in ACR, thus yielding more stable products. Findings of the present study highlighted certain classes of polyphenols as promising sequestering agents of R, -unsaturated aldehydes to inhibit or restrain carbonyl stress-associated diseases.