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

Chem Res Toxicol. 2009 Oct;22(10):1721-7. doi: 10.1021/tx900221s.


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

MeSH terms

  • Acrolein / chemistry*
  • Acrolein / toxicity
  • Aldehydes / chemistry*
  • Aldehydes / toxicity
  • Chromatography, Liquid
  • Cross-Linking Reagents / chemistry*
  • Cross-Linking Reagents / toxicity
  • Flavonoids / chemistry*
  • Lipid Peroxidation*
  • Molecular Conformation
  • Phenols / chemistry*
  • Phloretin / chemistry
  • Polyphenols
  • Tandem Mass Spectrometry


  • Aldehydes
  • Cross-Linking Reagents
  • Flavonoids
  • Phenols
  • Polyphenols
  • Acrolein
  • 4-hydroxy-2-nonenal
  • Phloretin