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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Research Article

Micro Composite Palmitoylethanolamide/Rutin Reduces Vascular Injury through Modulation of the Nrf2/HO−1 and NF-kB Pathways

Author(s): Roberta Fusco, Rosalba Siracusa, Enrico Gugliandolo, Alessio Filippo Peritore, Ramona D’Amico, Marika Cordaro, Rosalia Crupi, Daniela Impellizzeri, Chiara Gomiero, Salvatore Cuzzocrea* and Rosanna Di Paola*

Volume 28 , Issue 30 , 2021

Published on: 29 March, 2021

Page: [6287 - 6302] Pages: 16

DOI: 10.2174/0929867328666210329120213


Background: Vascular remodeling processes induced by acute and chronic injuries are characterized by inflammation and oxidative stress. In arteriosclerosis, atherosclerosis, and restenosis, the progression of neointimal hyperplasia is a key event of vascular damage.

Objective: Our study was aimed to investigate the inflammation and oxidative stress development during vascular impairment and the potential efficacy of treatment of new micro composite N-palmitoylethanolamine/Rutin at a ratio of 1:1 (PEA/RUT). The anti-inflammatory effects of Palmitoylethanolamide (PEA) are well known. Rutin has important pharmacological actions, including antioxidant and vasoprotective.

Methods: As a model of vascular injury, we used the complete ligature of the left carotid artery for fourteen days and administered PEA/RUT at the dose of 10 mg/Kg.

Results: This study demonstrated that after fourteen days of carotid ligation, there is a substantial structural change in the vessel morphology, with inflammatory cell infiltration and reactive oxygen species production. PEA/RUT administration reduced change in vascular morphology, cytokines like monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules expression like intercellular adhesion molecules-1 (ICAM-1), proinflammatory cytokines production (IL-1 β, IL-6 and TNF- α), oxidative and nitrosative stress (nitrotyrosine and PARP expression and NRF2 pathway).

Conclusion: Our data clearly demonstrate the beneficial effect of PEA/RUT administration in reducing inflammation, oxidative stress, and vascular damage.

Keywords: Vascular injury, inflammation, oxidative stress, Nrf2, NF-kB, rutin.

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