Rice bran enzymatic extract restores endothelial function and vascular contractility in obese rats by reducing vascular inflammation and oxidative stress

Abstract

Background

Rice bran enzymatic extract (RBEE) used in this study has shown beneficial activities against dyslipidemia, hyperinsulinemia and hypertension. Our aim was to investigate the effects of a diet supplemented with RBEE in vascular impairment developed in obese Zucker rats and to evaluate the main mechanisms mediating this action.

Methods and results

Obese Zucker rats were fed a 1% and 5% RBEE-supplemented diet (O1% and O5%). Obese and their lean littermates fed a standard diet were used as controls (OC and LC, respectively). Vascular function was evaluated in aortic rings in organ baths. The role of nitric oxide (NO) was investigated by using NO synthase (NOS) inhibitors. Aortic expression of endothelial NOS (eNOS), inducible NOS (iNOS), tumor necrosis factor (TNF)-α and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits and superoxide production in arterial wall were determined. Endothelial dysfunction and vascular hyperreactivity to phenylephrine in obese rats were ameliorated by RBEE treatment, particularly with 1% RBEE. Up-regulation of eNOS protein expression in RBEE-treated aortas should contribute to this activity. RBEE attenuated vascular inflammation by reducing aortic iNOS and TNF-α expression. Aortas from RBEE-treated groups showed a significant decrease of superoxide production and down-regulation of NADPH oxidase subunits.

Conclusion

RBEE treatment restored endothelial function and vascular contractility in obese Zucker rats through a reduction of vascular inflammation and oxidative stress. These results show the nutraceutical potential of RBEE to prevent obesity-related vascular complications.

Introduction

Occidental dietary habits have contributed to increased prevalence of obesity, type 2 diabetes mellitus and other pathologies included in the metabolic syndrome [1]. Obesity, in particular abdominal obesity, has been established as a primary contributor to acquired insulin resistance, as increasing adiposity is correlated with impaired insulin action. Endothelial dysfunction, an independent predictor of cardiovascular events [2], has been consistently associated with obesity and the metabolic syndrome [3] in a complex interplay with insulin resistance [4]. Nevertheless, it has been reported that vascular dysfunction of obesity is not only limited to the endothelium but also involves the smooth muscle cell layer, leading to an increased oxidative stress in the vascular wall and the subsequent deregulation of the main control mechanisms providing vascular homeostasis [5]. Vascular function impairment in the metabolic syndrome mainly implies an unbalance between the vasoprotective effect of endothelial nitric oxide (NO) and the unfavorable action of vasoconstrictor factors [e.g., endothelin-1 and reactive oxygen species (ROS)] and proinflammatory mediators [e.g. tumor necrosis factor (TNF)-α] [5]. The pathophysiology of obesity-related vascular dysfunction is therefore an important target for developing new therapeutic approaches aimed to ameliorate cardiovascular risk factors related to metabolic syndrome.

Numerous studies suggest that the first strategy in the prevention of disorders associated with obesity consists of including in the diet food or dietary components with functional properties [6], [7]. Rice, and particularly rice bran, is an excellent nutritional source of bioactive compounds, including high-healthy-value proteins and phytochemicals such as γ-oryzanol, sterols and tocols [8], [9]. Besides, phenolic compounds contained in rice bran, such as γ-oryzanol and ferulic acid, are known to provide strong antioxidant activities [10], [11]. The hypolipidemic, antioxidant and anti-inflammatory properties of the mixture of phytosteryl ferulates contained in γ-oryzanol make it a good candidate for health food [12], [13]. However, the therapeutic use of rice bran is limited because of the insolubility of its proteins and the integrity of its nutraceutical compounds. For this reason, rice bran oils have become commonly utilized in order to study its properties, despite the high risk of rancidity that it involves [14]. These limitations have been counteracted by the recent production of a water-soluble rice bran enzymatic extract (RBEE) [15] that provides numerous advantages over other rice bran derivatives regarding water solubility, increased content in nutraceutical compounds and lack of rancidity.

Our recent investigations have evidenced that a diet supplemented with RBEE is able to ameliorate cardiometabolic risk factors in obese Zucker rats, showing a remarkable action on dyslipidemia, moderate hypertension, insulin resistance and adiponectin levels [16]. However, the effect of RBEE on vascular dysfunction associated with obesity and the main mechanisms by which this rice bran derivative induces its beneficial action on cardiometabolic risk factors remain unknown. The potential of rice bran extracts on vascular alterations has only been recently suggested in a few in vitro investigations which evaluated the effects of γ-oryzanol and a rice bran ethyl acetate extract on adhesion molecules expression in vascular endothelial cells or hypertrophy in smooth muscle cells, respectively [17], [18].

Considering the beneficial effect of an RBEE-enriched diet on cardiometabolic parameters developed in obese rats, it is expected that RBEE will be able to restore endothelial dysfunction and vascular inflammation and oxidative stress associated with obesity in an animal model of metabolic syndrome. Thus, the aim of our study was to determine the capacity of a diet supplemented with RBEE to modify vascular dysfunction in obese Zucker rats and to identify the main pathways that could be implicated in the RBEE bioactivity. Elucidation of these vascular mechanisms might partially explain the beneficial action of RBEE treatment in cardiometabolic parameters of obese animals found in our previous investigations.