2026-04-17T14:18:16Zhttps://recercat.cat/oai/request

oai:recercat.cat:10256/207962024-06-18T12:41:44Zcom_2072_452955com_2072_2054col_2072_453079

2024-06-18T12:41:44Z urn:hdl:10256/20796 Computational de-orphanization of the olive oil biophenol oleacein: Discovery of new metabolic and epigenetic targets Cuyàs, Elisabet Castillo, David Llorach Parés, Laura Lozano Sánchez, Jesús Verdura, Sara Nonell-Canals, Alfons Brunet i Vidal, Joan Bosch Barrera, Joaquim Joven, Jorge Valdés Mas, Rafael Sanchez Martinez, Melchor Segura Carretero, Antonio Menéndez Menéndez, Javier Abel Epigenètica Epigenetics The health promoting effects of extra virgin olive oil (EVOO) relate to its unique repertoire of phenolic compounds. Here, we used a chemoinformatics approach to computationally identify endogenous ligands and assign putative biomolecular targets to oleacein, one of the most abundant secoiridoids in EVOO. Using a structure-based virtual profiling software tool and reference databases containing more than 9000 binding sites protein cavities, we identified 996 putative oleacein targets involving more than 700 proteins. We subsequently identified the high-level functions of oleacein in terms of biomolecular interactions, signaling pathways, and protein-protein interaction (PPI) networks. Delineation of the oleacein target landscape revealed that the most significant modules affected by oleacein were associated with metabolic processes (e.g., glucose and lipid metabolism) and chromatin-modifying enzymatic activities (i.e., histone post-translational modifications). We experimentally confirmed that, in a low-micromolar physiological range (<20 μmol/l), oleacein was capable of inhibiting the catalytic activities of predicted metabolic and epigenetic targets including nicotinamide N-methyltransferase, ATP-citrate lyase, lysine-specific demethylase 6A, and N-methyltransferase 4. Our computational de-orphanization of oleacein provides new mechanisms through which EVOO biophenols might operate as chemical prototypes capable of modulating the biologic machinery of healthy aging 2024-06-18T12:41:44Z 2024-06-18T12:41:44Z 2019-09 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion peer-reviewed http://hdl.handle.net/10256/20796 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.fct.2019.05.037 info:eu-repo/semantics/altIdentifier/issn/0278-6915 info:eu-repo/semantics/altIdentifier/eissn/1873-6351 Tots els drets reservats info:eu-repo/semantics/openAccess Elsevier © Food and Chemical Toxicology, 2019, vol. 131, art.núm.110529 Articles publicats (IdIBGi) Cuyàs, Elisabet Castillo, David Llorach Parés, Laura Lozano Sánchez, Jesús Verdura, Sara Nonell-Canals, Alfons Brunet i Vidal, Joan Bosch Barrera, Joaquim Joven, Jorge Valdés Mas, Rafael Sanchez Martinez, Melchor Segura Carretero, Antonio Menéndez Menéndez, Javier Abel 2019 Computational de-orphanization of the olive oil biophenol oleacein: Discovery of new metabolic and epigenetic targets Food and Chemical Toxicology 131 art.núm.110529