Insights on Phenolipids as inhibitors of lipid oxidation

Lipid oxidation represents a major degradative pathway that compromises food quality and shelf-life, while its occurrence in biological systems is a key mediator of oxidative stress associated with chronic diseases. Classical antioxidants, particularly polyphenols, are well-known for their radical-scavenging and metal-chelating properties; however, their significant hydrophilicity restricts their efficacy in lipid-rich environments. To overcome such challenges, there has been an increasing interest in amphiphilic antioxidants, which exist in nature as secondary metabolites of several plants, as well as are produced by some microorganisms. Accordingly, the in vitro synthesis of engineered molecules termed phenolipids, or lipophenols, has evolved. Phenolipids are synthesized by the covalent attachment of a phenolic moiety to a lipid chain via chemical, enzymatic, or chemo-enzymatic pathways. This structural design has been proposed to improve their localization at lipid-water interfaces, where oxidation usually initiates, hence potentially enhancing their antioxidant efficacy. Preliminary studies indicate that phenolipids may enhance the oxidative stability of lipid-based food systems and potentially promote the intestinal absorption, membrane incorporation, and tissue distribution of their phenolic domains, consequently strengthening their protective efficacy in vivo. Yet, most of the current information is limited to in vitro or preclinical stages, and the mechanisms of action, safety profiles, and long-term biological impacts are not clearly understood. Therefore, this thesis aims to give a critical review of current knowledge regarding phenolipids as unique lipid oxidation inhibitors, outlining their synthesis methods, physicochemical characteristics, and reported antioxidant effects in food and biological systems, while highlighting the existing gaps and future perspectives required for their broader application.