Rice Bran Phenolic Compounds Regulate Genes Associated with Antioxidant and Anti-Inflammatory Activity in Human Umbilical Vein Endothelial Cells with Induced Oxidative Stress.

Nancy Saji,Nidhish Francis,Lachlan J Schwarz,Christopher L Blanchard,Abishek B Santhakumar

doi:10.3390/ijms20194715

Abstract

Oxidative stress, inflammation and endothelial dysfunction are associated with the development of cardiovascular and metabolic diseases. Phenolic extracts derived from rice bran (RB) are recognised to have antioxidant and anti-inflammatory potential. However, the underlying mechanisms remain unknown. Therefore, this study aimed to evaluate the ability of RB-derived phenolic extracts to modulate genes associated with antioxidant and anti-inflammatory pathways in human umbilical vein endothelial cells (HUVECs) under induced oxidative stress conditions. HUVECs under oxidative stress were treated with varying concentrations of RB phenolic extracts (25–250 µg/mL). Using quantitative real-time polymerase chain reaction, the expression of candidate genes that regulate antioxidant and anti-inflammatory pathways were determined. This included nuclear factor erythroid 2-related factor 2 (Nrf2), nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO1), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), intercellular adhesion molecule 1 (ICAM1), endothelial nitric oxide synthase (eNOS), ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and ecto-5′-nucleotidase (CD73). Phenolic extracts derived from RB down-regulated the expression of four genes, ICAM1, CD39, CD73 and NOX4 and up-regulated the expression of another four genes, Nrf2, NQO1, HO1 and eNOS, indicating an antioxidant/ anti-inflammatory effect for RB against endothelial dysfunction.

Highlights

Endothelial dysfunction has been identified as a primary contributor to the progression of vascular disorders such as cardiovascular disease (CVD) and stroke [1]
This study demonstrated that phenolic compounds derived from rice bran (RB) have a concentration-dependent increase on nuclear factor erythroid 2-related factor 2 (Nrf2), nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO1) expression in H2O2 induced human umbilical vein endothelial cells (HUVECs) (Figure 2)
The present study demonstrates that the expression of endothelial nitric oxide synthase (eNOS) gradually increased with RB phenolic extracts, at 250 μg/mL under oxidative stress conditions, suggesting that phenolic compounds in RB ameliorate the oxidative stress in vascular endothelial cells

Summary

Introduction

Endothelial dysfunction has been identified as a primary contributor to the progression of vascular disorders such as cardiovascular disease (CVD) and stroke [1]. Several genes including nuclear factor erythroid 2-related factor 2 (Nrf2), nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO1), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), intercellular adhesion molecule 1 (ICAM1), endothelial nitric oxide synthase (eNOS), ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and ecto-5 -nucleotidase (CD73) regulate the production of ROS within the vasculature. NQO1, a cytosolic flavoenzyme, is expressed in tissues including epithelial, vascular endothelial and adipocytes [3], and HO1 is an enzyme involved in heme catabolism resulting in biliverdin, carbon monoxide and ferrous iron production [4]. Reduced expression and activity of cellular Nrf, NQO1 or HO1 results in a failure of antioxidant and cytoprotective enzymes to regulate appropriately under oxidative stress conditions and is associated with increased risk of CVD [3,4]. Reduced expression and activity of cellular Nrf, NQO1 or HO1 results in a failure of antioxidant and cytoprotective enzymes to regulate appropriately under oxidative stress conditions and is associated with increased risk of CVD [3,4]. eNOS, primarily found in vascular endothelial cells, is involved in regulating vascular tone and blood clotting by generating protective nitric oxide (NO) molecules in the vasculature [5], thereby preventing the increased ROS production in endothelial cells

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