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. • OliveNet 2.0 database consists of 669 compounds from Olea europea (n = 15 classes); • Compounds have been characterised and made publicly available online; • Evaluated pharmacokinetics of the additional phytoprostane and lipophenol classes; • Utilisation of OliveNet 2.0 demonstrated through molecular docking against MTHFR; • Luteolin-4’-O-rutinoside and β-hydroxyacteoside identified as potential modulators;