Artículo
Inhibition of Endothelial Inflammatory Response by HT-C6, a Hydroxytyrosol Alkyl Ether Derivative
Autor/es | Marrero, Ana Dácil
Castilla, Laura Bernal, Manuel Manrique, Inmaculada Posligua García, Joel D. Moya Utrera, Federico Porras Alcalá, Cristina Espartero Sánchez, José Luis Sarabia, Francisco Quesada, Ana R. Medina, Miguel Ángel Martínez Poveda, Beatriz |
Departamento | Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica |
Fecha de publicación | 2023 |
Fecha de depósito | 2023-09-11 |
Resumen | 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 ... 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 (VCAM1), intercellular cell adhesion molecule 1 (ICAM1), E-selectin (SELE), C-C motif chemokine ligand 2 and 5 (CCL2 and CCL5) 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. |
Agencias financiadoras | Ministerio de Ciencia e Innovación (MICIN). España Junta de Andalucía |
Identificador del proyecto | PID2022-138181OB-I00
PID2019-105010RB-I00 RTI2018-098296-BI00 IJC2018-037657-I UMA18-FEDERJA-220 PY20_00257 |
Ficheros | Tamaño | Formato | Ver | Descripción |
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Inhibition of Endothelial.pdf | 3.650Mb | [PDF] | Ver/ | |