In silico studies reveal the mechanisms behind the antioxidant and anti-inflammatory activities of hydroxytyrosol

Abstract

Hydroxytyrosol is one of the most important phytochemical constituents of olive oil and possesses a very interesting pharmacological profile ranging from antioxidant, antimicrobial, and anti-inflammatory to low density lipoproteins oxidation inhibition. The present study aims to shed light on the mechanisms behind the antioxidant and the anti-inflammatory activities of hydroxytyrosol. Towards the first aim, quantum mechanical calculations of several properties including bond dissociation energy, proton dissociation enthalpy, adiabatic ionization potential, proton affinity, and electron transfer enthalpy has been performed in vacuum and water environments in order to propose an antioxidant activity mechanism. Results support the hydrogen atom transfer mechanism as the most prevalent in gas phase, while in aqueous environment SPLET mechanism can explain the antioxidant mechanism of hydroxytyrosol. Towards the second aim, the potential of hydroxytyrosol to act as cyclooxygenase and lipoxygenase inhibitor against inflammation was examined through molecular docking studies. Cyclooxygenase is an enzyme, responsible for formation of prostanoids and its inhibition can provide relief from the symptoms of inflammation and pain. Lipoxygenases are a family of iron-containing enzymes involved in the metabolism of eicosanoids and their role in the regulation of pro-inflammatory responses has been well documented. Results indicate the binding mode in which hydroxytyrosol may exert its activity through lipoxygenase enzyme. Moreover, hydroxytyrosol can act as a core structure for bio-inspired inhibitors and may provide information for the design of dual cyclooxygenase/lipoxygenase inhibitors against inflammation.