Cucumis sativus Aqueous Fraction Inhibits Angiotensin II-Induced Inflammation and Oxidative Stress In Vitro.

Celeste Trejo-Moreno,Aida Castillo,Alejandro Zamilpa,Omar Medina-Campos,Gabriela Rosas-Salgado,Gladis Fragoso,Fernando Esquivel-Guadarrama,Maria Perez-Garcia,José Pedraza-Chaverri,Jacquelynne Cervantes-Torres,María Santana,Enrique Jiménez-Ferrer,Marisol Méndez-Martínez

doi:10.3390/nu10030276

Abstract

Inflammation and oxidative stress play major roles in endothelial dysfunction, and are key factors in the progression of cardiovascular diseases. The aim of this study was to evaluate in vitro the effect of three subfractions (SFs) from the Cucumis sativus aqueous fraction to reduce inflammatory factors and oxidative stress induced by angiotensin II (Ang II) in human microvascular endothelial cells-1 (HMEC-1) cells. The cells were cultured with different concentrations of Ang II and 0.08 or 10 μg/mL of SF1, SF2, or SF3, or 10 μmol of losartan as a control. IL-6 (Interleukin 6) concentration was quantified. To identify the most effective SF combinations, HMEC-1 cells were cultured as described above in the presence of four combinations of SF1 and SF3. Then, the effects of the most effective combination on the expression of adhesion molecules, the production of reactive oxygen species (ROS), and the bioavailability of nitric oxide (NO) were evaluated. Finally, a mass spectrometry analysis was performed. Both SF1 and SF3 subfractions decreased the induction of IL-6 by Ang II, and C4 (SF1 and SF3, 10 μg/mL each) was the most effective combination to inhibit the production of IL-6. Additionally, C4 prevented the expression of adhesion molecules, reduced the production of ROS, and increased the bioavailability of NO. Glycine, arginine, asparagine, lysine, and aspartic acid were the main components of both subfractions. These results demonstrate that C4 has anti-inflammatory and antioxidant effects.

Highlights

Inflammation and oxidative stress are two significant hallmarks of endothelial dysfunction and play a critical role in the pathogenesis of circulatory disorders such as hypertension, coronary artery disease, chronic heart failure, peripheral artery disease, and chronic renal failure
Our results indicate that human microvascular endothelial cells-1 (HMEC-1) cells expressed both adhesion molecules in the presence of angiotensin II (Ang II) 1000 and 5000 nM
Inflammation and oxidative stress are strongly associated with the progression of endothelial dysfunction; in turn, the latter is the physiopathological substrate of several cardiovascular diseases with high impact on mortality indices such as myocardial infarction, cerebrovascular disease, and chronic renal failure [33,34,35]

Summary

Introduction

Inflammation and oxidative stress are two significant hallmarks of endothelial dysfunction and play a critical role in the pathogenesis of circulatory disorders such as hypertension, coronary artery disease, chronic heart failure, peripheral artery disease, and chronic renal failure. The presence of ROS is detected by proteins sensitive to the redox status of the cell; in turn, these proteins activate AKT (Protein kinase B), MAPKs (mitogen-activated protein kinases), and NF-κB (Nuclear factor kappa B) [7,8,9,10], triggering inflammation and promoting the synthesis of IL-1β, IL-6, TNF-α, C reactive protein, E-selectin, ICAM-1 (Intercellular Adhesion Molecule 1), VCAM-1 (Vascular cell adhesion protein 1), and MCP-1 (Monocyte chemoattractant protein-1), among other molecules [11,12,13,14]

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