OliveNet 2.0: Chemical library of compounds from Olea europaea and utilisation for in silico modelling in the context of metabolic disorders targeting the MTHFR protein

The health-promoting effects of the Mediterranean diet have been extensively explored. Olive oil is the main source of dietary fat, with extra-virgin olive oil (EVOO) providing a rich source of bioactive compounds. The molecular mechanisms of action of a relatively small selection of olive-derived compounds, such as hydroxytyrosol, oleocanthal, and oleuropein, have been investigated in models of human disease. The OliveNet™ database, which is a comprehensive library of compounds derived from Olea europaea, was published in 2018. The compounds were identified and characterised from an extensive literature search. In this study, we present the OliveNet 2.0 database that supersedes the OliveNet™ library. In addition to the 13 classes that were originally in the OliveNet™ database, OliveNet 2.0 is composed of the phytoprostane and lipophenol classes (total of 669 compounds, 15 main classes). The OliveNet 2.0 database can be accessed through our publicly available website (https://epimedlab.org/olivenet-2-0/). Furthermore, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the phytoprostanes and lipophenols were evaluated in silico. To demonstrate an application of the OliveNet 2.0 database, molecular docking was performed to evaluate the binding characteristics of the olive-derived compounds against the C-regulatory domain of 5,10-methylenetetrahydrofolate reductase (MTHFR). The binding affinities and protein-ligand interactions of the olive-derived compounds were compared to the control compounds, which allosterically modulate the activity of MTHFR. Based on the results, the potential modulatory activity of β-hydroxyacteoside and luteolin-4'-O-rutinoside warrants further investigation. Overall, OliveNet 2.0 can be used to gain further insight into the mechanisms of action of olive-derived compounds.