Antioxidant, Immunostimulatory, and Anticancer Properties of Hydrolyzed Wheat Bran Mediated through Macrophages Stimulation

Abstract

Previous studies demonstrated that enzymatic hydrolysis enhances wheat bran (WB) biological properties. This study evaluated the immunostimulatory effect of a WB hydrolysate (HYD) and a mousse enriched with HYD (MH) before and after in vitro digestion on murine and human macrophages. The antiproliferative activity of the harvested macrophage supernatant on colorectal cancer (CRC) cells was also analyzed. MH showed significantly higher content than control mousse (M) in soluble poly- and oligosaccharides (OLSC), as well as total soluble phenolic compounds (TSPC). Although in vitro gastrointestinal digestion slightly reduced the TSPC bioaccessibility of MH, ferulic acid (FA) levels remained stable. HYD showed the highest antioxidant activity followed by MH, which demonstrated a greater antioxidant activity before and after digestion as compared with M. RAW264.7 and THP-1 cells released the highest amounts of pro-inflammatory cytokines after being treated with 0.5 mg/mL of digested WB samples. Treatment with digested HYD-stimulated RAW264.7 supernatant for 96 h showed the most anticancer effect, and spent medium reduced cancer cell colonies more than direct WB sample treatments. Although a lack of inner mitochondrial membrane potential alteration was found, increased Bax:Bcl-2 ratio and caspase-3 expression suggested activation of the mitochondrial apoptotic pathway when CRC cells were treated with macrophage supernatants. Intracellular reactive oxygen species (ROS) were positively correlated with the cell viability in CRC cells exposed to RAW264.7 supernatants (r = 0.78, p < 0.05) but was not correlated in CRC cells treated with THP-1 conditioned media. Supernatant from WB-stimulated THP-1 cells may be able to stimulate ROS production in HT-29 cells, leading to a decrease of viable cells in a time-dependent manner. Therefore, our present study revealed a novel anti-tumour mechanism of HYD through the stimulation of cytokine production in macrophages and the indirect inhibition of cell proliferation, colony formation, and activation of pro-apoptotic proteins expression in CRC cells.

Effects of Dietary Supplementation with a Ferulic Acid-Rich Bioactive Component of Wheat Bran in a Murine Model of Graft-Versus-Host Disease

“…Hydrolyzed WB was produced through the optimization of novel strategies to yield the highest concentration of soluble phenolic compounds, thereby maximizing the antioxidant and anti-inflammatory potential of the WB. Our previous studies have shown a reduction in TNF-α production in LPS-induced murine macrophages in the presence of this WB ingredient and an increased trend in most of the antioxidant parameters [8][9][10][11]. Other studies have also demonstrated, both in vitro and in vivo, the anti-inflammatory effects of FA.…”

“…To improve the bioaccessibility, bioavailability, and ultimate bioactivity of this compound, our group has developed new technological strategies involving enzymatic hydrolysis combined with thermomechanical treatments. These approaches are designed to increase the ratio of free to bound FA content in WB, improving also their antioxidant and anti-inflammatory properties in vitro [10,11].…”

Boosting Synergistic Antioxidant and Anti-Inflammatory Properties Blending Cereal-Based Nutraceuticals Produced Using Sprouting and Hydrolysis Tools

“…Alternatively, enzymatic hydrolysis is another strategy, which, through the combination of cellulolytic and xylanolytic enzymes, can depolymerize the β-D-(1→4)-glucosidic and β-D-(1→4)-xylosidic bonds [ 33 ]. Different authors have determined that enzymatic hydrolysis allows the degradation of cell wall fibers, increasing the availability of phenolic compounds and β-glucan [ 20 , 25 , 34 ].…”