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 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.

Acrolein scavengers: Reactivity, mechanism and impact on health

“…Similar polyphenols have also been documented as effective trapping agents of ACR [118][119][120]. In a screening of 21 natural polyphenols, it was found that nine of them (1 mM) directly quenched ACR (0.5 mM) by 27.4-99.6% under simulated physiological conditions (0.01 M PBS, pH 7.4, 371C) with 90 min incubation.…”

“…Examination of the structure-activity relationship showed that a phloroglucinol moiety (usually called an A ring in these structures) was shared among all the effective scavengers, suggesting the importance of this skeleton for trapping of ACR [119]. Furthermore, substitution of any of the hydroxyl groups in A ring weakened the activities for electrophilic aromatic substitution, therefore lowering the trapping effects [120].…”

2-Acetylcyclopentanone, an Enolate-Forming 1,3-Dicarbonyl Compound, Is Cytoprotective in Warm Ischemia-Reperfusion Injury of Rat Liver

“…Enolate Hepatoprotection in Ischemia-Reperfusion adducts with acrolein, HNE, and other electrophilic unsaturated aldehydes that participate in oxidative stress-induced injury (LoPachin et al, 2011). Similarly, curcumin and other phytopolyphenols (e.g., phloretin, resveratrol) can ionize to form nucleophilic enolate sites that scavenge electrophilic aldehydes (Awasthi et al, 1996;Zhu et al, 2009Zhu et al, , 2012.…”

Secondary Plant Metabolites for Sun Protective Cosmetics: From Pre-Selection to Product Formulation

“…Oxidation end-products of sebum and keratinocyte cell membrane lipid moieties represent key biochemical mediators of the inflammatory reaction induced by UV irradiation [1,73,74], among which 4-hydroxynonenal (4-HNE) is the most thoroughly characterised. Green tea polyphenols, theaflavins, and other SPMs could act as sacrificial nucleophiles trapping 4-HNE efficiently, the reason why tea and red wine polyphenols protect various types of cells in vitro, against HNE-induced intracellular oxidative stress and cytotoxicity [75]. In addition, a significant inhibition of HNE-induced mitochondrial ROS production is provided by quercetin, epigallocatechin gallate (EGCG), theaflavins and their gallate esters [76].…”