Chemical evaluation of arbequina extra virgin olive oil with in silico analysis of its key phenolic compounds targeting LDL metabolism

The chemical properties of extra virgin olive oil (EVOO) from Arbequina variety grown in Türkiye were evaluated, and its major phenolic compounds (PC) (oleocanthal, oleacein, luteolin and tyrosol) were compared with drugs (bempedoic acid and ezetimibe) involved in LDL metabolism through in silico analyses. The fatty acids composition (FA), PC and volatile organic compound (VC) profiles of EVOO obtained from Arbequina olive were evaluated via chromatographic methods (GC-FID, HPLC). The quality parameters, including total phenolic content (TPC), pigment content, peroxide value (PV), free fatty acid levels (FFA) and absorption coefficients, were determined via spectrophotometric methods. ADMET profiles, density functional theory (DFT), molecular docking, and the biological targets and activities of oleocanthal, oleacein, luteolin, tyrosol, bempedoic acid and ezetimibe were calculated and compared. Oleocanthal, oleacein, and luteolin completely passed the rules of Lipinski, Ghose, Veber, Egan, and Muegge, whereas only luteolin met the optimum ranges of all the criteria on the radar map. All 4 PC strongly inhibited OATP1B1 and OATP1B3, whereas oleocanthal, oleacein, and luteolin inhibited CYP3A4. Additionally, luteolin, oleocanthal and ezetimibe had individual inhibitory effects on CYP1A2, CYP2C9 and CYP2D6, respectively. Oleacein had the best binding affinity for LDLR, whereas luteolin had the best binding affinity for PCSK9 and ACLY. Oleacein was biologically effective against pathogens such as Leishmania species, but showed high reactivity with a low energy gap and high malleability. In conclusion, oleacein, oleocanthal and luteolin have potential therapeutic functions in LDL metabolism, which plays a role in atherosclerosis. However, experimental and clinical studies are needed for more evidence.