Mechanistic insights into the bioavailability of oleocanthal and oleacein from olive oil in presence of wine active peptides and amino acids

Abstract

Oleocanthal (OC) and oleacein (OL) are highly bioactive secoiridoids found in olive oil at elevated concentrations, especially when it is produced from unripe olives (Olea europaea L.). Both compounds have been correlated with strong activities against serious diseases through recent clinical trials. The most important clinical trials have been performed in patients against chronic lymphocytic leukemia1, against mild cognitive impairment2 and against platelet aggregation of normal3 or diabetic patients. Carefully designed nutritional interventions in humans using olive oil with high OC/OL content or olive oil without OC/OL have provided strong evidence about the unique therapeutic role of those compounds. However, both compounds do not actually circulate in the body and cannot be found in any biological fluid. Recent studies have shown that OC and OL react spontaneously with plasma aminoacids like glycine to form new highly bioactive chemical entities like oleoglycine that circulate in the blood and can also reach the brain of experimental animals4. During our continuous effort to understand the mechanisms of action of OC/OL, we investigated the reactions of both compounds with aminoacids and peptides found in white wines5. During this study we screened the selectivity and the rate of this reaction, and we discovered new metabolites with unique structures and properties like oleocysteine (1a,b), oleoserine (2a,b) or oleoglutathione (3a,b). The synthesized metabolites were structurally elucidated using NMR and MS. OC/OL selectivity was assessed by competitive nucleophilic addition reactions with peptides and amino acids at pH=7 and 3.5, quantifying products and ratios by UHPLC-Q-ToF MS. The obtained results can shed light on the mechanism of action of OC/OL and more significantly explain their bioavailability.

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