Rice Bran Phenolic Extracts Modulate Insulin Secretion and Gene Expression Associated with ß-Cell Function.

Oxidative stress is known to modulate insulin secretion and initiate gene alterations resulting in impairment of ß-cell function and type 2 diabetes mellitus (T2DM). Rice bran (RB) phenolic extracts contain bioactive properties that may target metabolic pathways associated with the pathogenesis of T2DM. This study aimed to examine the effect of stabilized RB phenolic extracts on the expression of genes associated with ß-cell function such as glucose transporter 2 (Glut2), pancreatic and duodenal homeobox 1 (Pdx1), sirtuin 1 (Sirt1), mitochondrial transcription factor A (Tfam), and insulin 1 (Ins1) in addition to evaluating its impact on glucose-stimulated insulin secretion. It was observed that treatment with different concentrations of RB phenolic extracts (25-250 µg/mL) significantly increased the expression of Glut2, Pdx1, Sirt1, Tfam, and Ins1 genes and glucose-stimulated insulin secretion under both normal and high glucose conditions. RB phenolic extracts favourably modulated the expression of genes involved in ß-cell dysfunction and insulin secretion via several mechanisms such as synergistic action of polyphenols targeting signalling molecules, decreasing free radical damage by its antioxidant activity, and stimulation of effectors or survival factors of insulin secretion.

Black Sorghum Phenolic Extract Modulates Platelet Activation and Platelet Microparticle Release.

Platelet hyper-activation and platelet microparticles (PMPs) play a key role in the pathogenesis of cardiovascular diseases. Dietary polyphenols are believed to mimic antiplatelet agents by blunting platelet activation receptors via its antioxidant phenomenon. However, there is limited information on the anti-platelet activity of grain-derived polyphenols. The aim of the study is to evaluate the effects of sorghum extract (Shawaya short black 1 variety), an extract previously characterised for its high antioxidant activity and reduction of oxidative stress-related endothelial dysfunction, on platelet aggregation, platelet activation and PMP release. Whole blood samples collected from 18 healthy volunteers were treated with varying non-cytotoxic concentrations of polyphenol-rich black sorghum extract (BSE). Platelet aggregation study utilised 5 µg/mL collagen to target the GPVI pathway of thrombus formation whereas adenine phosphate (ADP) was used to stimulate the P2Y1/P2Y12 pathway of platelet activation assessed by flow cytometry. Procaspase-activating compound 1 (PAC-1) and P-selectin/CD62P were used to evaluate platelet activation- related conformational changes and degranulation respectively. PMPs were isolated from unstimulated platelets and quantified by size distribution and binding to CD42b. BSE treatment significantly reduced both collagen-induced platelet aggregation and circulatory PMP release at 40 µg/mL (p < 0.001) when compared to control. However, there was no significant impact of BSE on ADP-induced activation-dependent conformational change and degranulation of platelets. Results of this study suggest that phenolic rich BSE may confer cardio-protection by modulating specific signalling pathways involved in platelet activation and PMP release.

The anti-inflammatory and antioxidant effects of acute consumption of pigmented rice in humans.

The pathogenesis of lifestyle diseases has been significantly correlated to high levels of oxidative stress and pro-inflammation. The antioxidant and anti-inflammatory properties of polyphenols in coloured rice varieties could have potential to neutralize oxidative stress and modulate inflammatory responses. A cross-over design, randomised, dietary intervention human clinical trial was conducted on a pre-screened healthy population (n = 24) investigating the antioxidant and anti-inflammatory potential of pigmented rice (purple, red and brown) varieties. Post baseline blood samples collection volunteers consumed a serve of cooked pigmented rice. Blood samples were collected at 30-minutes, 1, 2 and 4-hours post rice consumption. A one-week wash-out period between each supplementation bout (rice variety) was conducted. Blood and biochemical parameters were analysed on baseline blood samples. Antioxidant activity, malondialdehyde (MDA) and a pro-inflammatory cytokine panel were analysed on the blood samples collected. Post purple rice consumption, antioxidant activity increased (p < 0.0001) by 70.5% and maintained elevated for all time points. The red rice variety Yunlu29, significantly (p < 0.005) reduced MDA levels by 9.2% at the 30-minute time point. Purple rice demonstrated a significant (p < 0.05) decrease by 4.0% at the 30-minute time point only. Purple rice significantly decreased TNF-α levels at the 1-hour (p < 0.05) and 4-hour (p < 0.005) time points by 21.9% and 25.4% respectively. IL-6 concentrations were significantly reduced at 1 and 2-hour post Purple (p < 0.05; 11.7%) and Yunlu29 (red) (p < 0.01; 14.1%) consumption respectively. The brown rice variety did not affect any parameters tested. The outcomes of this study, highlight that polyphenols found in pigmented rice may play a key role in targeting specific oxidative stress and inflammatory therapeutic pathways. Pigmented rice varieties may serve as a potential functional food in reducing risk factors associated with lifestyle diseases.

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

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.

Coloured rice-derived polyphenols reduce lipid peroxidation and pro-inflammatory cytokines ex vivo.

Rice-derived polyphenols have been demonstrated to alleviate obesity-related oxidative stress and inflammation. The aim of the study was to investigate if coloured rice polyphenol extracts (PE) reduce malondialdehyde, interleukin-6 and tumour necrosis factor-α (TNF-α) levels in obese individuals ex vivo. Malondialdehyde and pro-inflammatory cytokines were quantified using high-performance liquid chromatography and flow cytometry respectively. Fasting blood samples were treated with PE from three coloured rice varieties (purple, red and brown rice) at varying concentrations (10, 20, 50, 100, 200 and 500 µg mL-1). PE treatment demonstrated a dose-dependent reduction in malondialdehyde and TNF-α levels. Purple PE reduced plasma malondialdehyde concentration by 59% compared to red (21%) and brown (25.5%) rice PE. Brown rice PE at 50 µg mL-1 reduced TNF-α levels by 98% compared to red (80%) and purple rice PE (74%). Rice PE did not modulate plasma interleukin-6 concentrations. Coloured rice may be of therapeutic benefit as a potential functional food alternative in targeting specific pathways associated with obesity.

The effect of anthocyanin supplementation in modulating platelet function in sedentary population: a randomised, double-blind, placebo-controlled, cross-over trial.

The anti-thrombotic properties of anthocyanin (ACN) supplementation was evaluated in this randomised, double-blind, placebo (PBO) controlled, cross-over design, dietary intervention trial in sedentary population. In all, sixteen participants (three males and thirteen females) consumed ACN (320 mg/d) or PBO capsules for 28 d followed by a 2-week wash-out period. Biomarkers of thrombogenesis and platelet activation induced by ADP; platelet aggregation induced by ADP, collagen and arachidonic acid; biochemical, lipid, inflammatory and coagulation profile were evaluated before and after supplementation. ACN supplementation reduced monocyte-platelet aggregate formation by 39 %; inhibited platelet endothelial cell adhesion molecule-1 expression by 14 %; reduced platelet activation-dependant conformational change and degranulation by reducing procaspase activating compound-1 (PAC-1) (↓10 %) and P-selectin expression (↓14 %), respectively; and reduced ADP-induced whole blood platelet aggregation by 29 %. Arachidonic acid and collagen-induced platelet aggregation; biochemical, lipid, inflammatory and coagulation parameters did not change post-ACN supplementation. PBO treatment did not have an effect on the parameters tested. The findings suggest that dietary ACN supplementation has the potential to alleviate biomarkers of thrombogenesis, platelet hyperactivation and hyper-aggregation in sedentary population.