Bioaccessible Phenolic Alkyl Esters of Wine Lees Decrease COX-2-Catalyzed Lipid Mediators of Oxidative Stress and Inflammation in a Time-Dependent Manner

Lipophenols, phenolic compounds esterified with fatty alcohols or fatty acids, provide greater health benefits upon dietary ingestion of plant-based foods than unesterified (poly)phenols. Based on this premise, the present study aimed to demonstrate the role of gastrointestinal enzymes (pepsin, pancreatin, and pancreatic lipase) in releasing alkyl gallates and <i>trans</i>-caffeates from wine lees, providing bioactive compounds with enhanced capacities against oxidative stress (OS) and para-inflammation. The UHPLC-ESI-QqQ-MS/MS-based analysis revealed ethyl gallate and ethyl <i>trans</i>-caffeate as the most prominent compounds (1.675 and 0.872 μg/g dw, respectively), while the bioaccessibility of the derivatives of gallic and caffeic acids was dependent on the alkyl chain properties. The <i>de novo</i> formation of alkyl gallates during gastric and intestinal digestion resulted from intestinal enzyme activity. Moreover, the <i>in vitro</i> capacity of bioaccessible alkyl esters of gallic and <i>trans</i>-caffeic acids to reduce cyclooxygenase-2 concentration and modulate oxilipins related to OS (8-iso-PGF_2α) and inflammation (PGF_2α and PGE₂) was demonstrated in a time-dependent manner. In conclusion, the presence of alkyl esters of gallic and <i>trans</i>-caffeic acids in wine lees and their subsequent formation during digestion of this byproduct emphasize their value as a source of antioxidant and anti-inflammatory compounds, encouraging the consideration of wine lees as a valuable ingredient for health-promoting coproducts.