Unravelling the capacity of hydroxytyrosol and its lipophenolic derivates to modulate the H2O2-induced isoprostanoid profile of THP-1 monocytes by UHPLC-QqQ-MS/MS lipidomic workflow

Presently, the attention given to natural substances to counteract damage produced by oxidative stress (OS) has risen sharply. In this scenario, hydroxytyrosol (HT) derivatives, formed as a result of HT conjugation with fatty acids (FAs) (lipophenols), have been recently described in foodstuffs such as extra virgin olive oil, as being powerful bioactive compounds with a higher activity than the unesterified phenolic compound. The present work describes the capacity of HT lipophenols to act on the course of OS and secondary inflammatory processes, based on their capacity to modulate the isoprostanoid profile induced by HO in THP-1 monocytic cells. A UHPLC-QqQ-ESI-MS/MS-based lipidomics workflow was applied over a range of 37 human oxylipins. The main outcomes retrieved suggest both HT and HT-lipophenols as regulators of the cellular redox balance, acting as pro-oxidants in vitro, which is highly dependent on the experimental conditions. Our outcomes suggest the anti-inflammatory potential of both HT and HT-lipophenols, where the type of the FAs on the HT core appears to be critical for defining the bioactivity of lipophenols, highlighting that a lipidomic approach, with the simultaneous analysis of multiple oxylipins, is critical for the understanding of the bioactivity of lipophenols on isoprostanoid generation and hence, on pathophysiological processes.
This work was partially funded by the “Fundación Séneca de la Región de Murcia” Grupo de Excelencia 19900/GERM/15 and the Spanish project AGL2017-83386-R-AEI/FEDER, UE from the Spanish Ministry of Science, Innovation, and Universities. SM was supported by a Postdoctoral Contract (Saavedra-Fajardo 21078/SF/19) from the Agency for Science and Technology of the Región de Murcia – “Fundación Séneca” (Spain)