Natural polyphenols as direct trapping agents of lipid peroxidation-derived acrolein and 4-hydroxy-trans-2-nonenal

Abstract

Acrolein (ACR) and 4-hydroxy-trans-2-nonenal (HNE) are two cytotoxic lipid-derived α,β-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 C=C double bond of ACR, followed by the formation of hemiacetal between the hydroxyl group in the A ring of phloretin and the C=O carbonyl group in ACR, thus yielding more stable products. Findings of the present study highlighted certain classes of polyphenols as promising sequestering agents of α,β-unsaturated aldehydes to inhibit or restrain carbonyl stress-associated diseases. © 2009 American Chemical Society.