Inhibition of Endothelial Inflammatory Response by HT-C6, a Hydroxytyrosol Alkyl Ether Derivative

• Main Authors: Ana Dácil Marrero (Author), Laura Castilla (Author), Manuel Bernal (Author), Inmaculada Manrique (Author), Joel D. Posligua-García (Author), Federico Moya-Utrera (Author), Cristina Porras-Alcalá (Author), José Luis Espartero (Author), Francisco Sarabia (Author), Ana R. Quesada (Author), Miguel Ángel Medina (Author), Beatriz Martínez-Poveda (Author)
• Format: Book
• Published: MDPI AG, 2023-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antiox12081513; 2076-3921
• Keywords: hydroxytyrosol; hydroxytyrosol derivatives; inflammatory response; endothelial cells; NF-κB; HT-C6; Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 12, Iss 8, p 1513 (2023)

Hydroxytyrosol (HT) is a bioactive phenolic compound naturally present in olives and extra virgin olive oil (EVOO) which is described as an antioxidant, antitumoral and antiangiogenic molecule. Previous studies of semi-synthetic HT-derivatives presented the hydroxytyrosyl alkyl ether HT-C6 as one of the most potent derivatives studied in the context of antioxidant, anti-platelet and antiangiogenic assays, but its direct effect on inflammation was not reported. In this work, we use RT-qPCR measure of gene expression, protein analysis by Western-blot and immunofluorescence techniques, adhesion and migration functional assays and single-cell monitoring of reactive oxygen species (ROS) in order to explore in vitro the ability of HT-C6 to interfere in the inflammatory response of endothelial cells (ECs). Our results showed that HT-C6 strongly reduces the TNF-α-induced expression of vascular cell adhesion molecule 1 (<i>VCAM1</i>), intercellular cell adhesion molecule 1 (<i>ICAM1</i>), E-selectin (<i>SELE</i>), C-C motif chemokine ligand 2 and 5 (<i>CCL2</i> and <i>CCL5</i>) in HUVECs, impairing the chemotactic and adhesion potential of these cells towards THP-1 monocytes in vitro. In this work, we define a mechanism of action underlying the anti-inflammatory effect of HT-C6, which involves the abrogation of nuclear factor kappa B (NF-κB) pathway activation in ECs. These results, together with the ability of HT-C6 to reduce ROS formation in ECs, point to this compound as a promising HT-derivative to be tested in the treatment of atherosclerosis.