Search

Background: Coffeeberry extract, rich in chlorogenic acids, shows promise in improving mood and cognition, particularly when co-supplemented with phenolic compounds. However, limited work has considered the effects of coffeeberry in isolation, especially at low doses. Objective: The current study investigated the effect of low and moderate doses of coffeeberry extract on cognition and mood. Design: This randomized, double-blind, placebo-controlled crossover design investigated three active beverages on a sample of 72 healthy adults aged 18–49 years. The investigational beverages contained 100 mg or 300 mg coffeeberry extract (standardized to 40% chlorogenic acid), or 75 mg caffeine (positive control). Cognition, mood, and subjective energy were measured at baseline and then again at 60 and 120 min post-treatment. Results: Analysis revealed no effect of 300 mg coffeeberry extract, while 100 mg resulted in increased mental fatigue during the performance of cognitively demanding tasks (p = 0.025) and decreased accuracy on a task of sustained attention (p = 0.003), compared to placebo, at 60 min post dose. Conclusions: Administration of 100 mg and 300 mg coffeeberry extracts revealed limited, transient negative effects following 100 mg coffeeberry. Given the large number of outcome measures analysed and the absence of findings following the 300 mg dose, these negative findings should be interpreted with caution. Overall, the findings of the current study suggest that coffeeberry extract at a low or moderate dose does not have a beneficial effect on mood, mental and physical energy levels, or cognition; higher doses, as have been administered previously, may be more effective.

Oat has procured its acclaim as a health promoting food partially due to its positive effect on glucose control. It has been demonstrated that oat β-glucan can interfere with postprandial glucose response. A large majority of this action is attributed to the increase in viscosity due to the β-glucan content in oat foods. While it is known that an increase in viscosity due to higher molecular weight of β-glucan can improve its glycemic effects, it is not known if an increase in viscosity attained by processing variables can further enhance the positive effect of oat on glucose control. In the current study we have examined the effect of kilning, tempering, microwaving, cooking, soaking and flaking on oat β-glucan viscosity. An acute randomized crossover clinical trial was also conducted to test oatmeal products containing low, medium and high β-glucan viscosity for their effect on postprandial glycemic response. Results from the processing experiments demonstrate that kilned samples, when tempered to 25% moisture and microwaved for 2 minutes, can produce much higher final viscosity compared to other samples with similar β-glucan content, molecular weight and solubility. However, results from the clinical trial show that the increase in the viscosity of the oat β-glucan attained through processing in this study did not have any effect on postprandial glucose control.

BACKGROUND Oats are a whole grain cereal with potentially favorable effects on the postprandial glycemic response; however, the effects of oat processing on these glycemic benefits are not well understood. OBJECTIVES The study objective was to determine the effects of differently processed oats on the postprandial blood glucose and insulin responses relative to refined grains. METHODS Eleven electronic databases were systematically searched to identify studies published up to and including May 2019. Randomized controlled trials comparing the postprandial blood glucose and insulin responses to oats compared with any refined grain were included, so long as the available carbohydrate content of the test meals was similar. Pooled effect sizes were computed using the difference in incremental area under the curves for blood glucose and insulin following the consumption of oats compared with the refined grain control. RESULTS Ten publications were included, with intact oat kernels studied in 3 comparisons, thick oat flakes (>0.6 mm) in 7 comparisons, and thin/quick/instant oat flakes (≤0.6 mm) in 6 comparisons. Compared with the consumption of the refined grain control, the consumption of intact oat kernels was associated with significant reductions in postprandial blood glucose (-45.5 mmol x min/L; 95% CI: -80.1, -10.9 mmol x min/L; P = 0.010) and insulin (-4.5 nmol x min/L; 95% CI: -7.1, -1.8 nmol x min/L; P = 0.001) responses; the consumption of thick oat flakes was associated with significant reductions in postprandial blood glucose (-30.6 mmol x min/L; 95% CI: -40.4, -20.9 mmol x min/L; P

Milk protein concentrate (MPC; 0 g, 5 g, and 10 g) was added to two commercially available oat products (instant oats and steel cut oats) to examine how MPC addition, and consequent changes in meal formulation, manipulates both gastric lumen viscosity and intestinal carbohydrate-digestion kinetics, in vitro. We used the TNO Intestinal Model-1 (TIM-1) to simulate gastrointestinal digestion of the oats-based meals. Meals containing 5 g or 10 g MPC yielded significantly less total bioaccessible sugar compared with those containing 0 g MPC, while the rate of starch digestion was significantly higher in meals containing 5 g or 10 g MPC. The TIM-1 was coupled with fluorescence spectroscopy and a luminescent molecular rotor to report changes in gastric viscosity in situ, showing that the gastric viscosity was higher in the meals containing MPC. Those findings suggest that MPC in oats-based meals significantly modifies the kinetics of carbohydrate digestion and increases gastric viscosity.

Reducing the glycaemic response to carbohydrate-containing foods may have desirable physiological effects for many people. Here, we aimed to determine the minimum amount of oat β-glucan from oat-bran which, when added to instant-oatmeal, would reduce the glycaemic response by 20% compared to a β-glucan-free cereal. Therefore, the glycaemic responses elicited by one serving (27 g) instant-oatmeal plus 247 g 2% milk (IO, 28 g available-carbohydrate, 1.2 g β-glucan) or IO plus 0.2, 0.4, 0.8 or 1.6 g oat β-glucan (OBG) from oat-bran, or an available-carbohydrate matched portion of cream of rice (CR) plus milk were measured over 2 h in n = 40 subjects using a randomized, cross-over design. The primary endpoint was incremental area under the curve (iAUC). The secondary endpoint was glucose peak-rise. The results showed that grams OBG consumed were significantly correlated with mean iAUC (p = 0.009) and with mean glucose peak-rise (p = 0.002). Each gram of OBG reduced iAUC by 7% and peak-rise by 15%. Thus, to achieve a ≥20% reduction in iAUC relative to CR, 1.6 g OBG had to be added to IO (74 ± 7 vs. 93 ± 6 mmol min L−1, p < 0.05), but, to achieve a 20% reduction in peak-rise, only 0.4 g OBG was required (2.00 ± 0.1 vs. 2.40 ± 0.1 mmol, p < 0.05). We conclude that adding OBG to IO flattened postprandial glycaemic responses in a dose-dependent fashion; 1.6 g OBG was required to reduce iAUC by ≥20% versus CR, but a 20% reduction in peak-rise required only 0.4 g. The greater effect of OGB on peak-rise than iAUC presumably reflects the way viscous dietary fibres modulate glucose absorption kinetics.

Three commercially available oat products—instant oats, steel cut oats, and oat bran—were studied using the TNO Intestinal Model-1 (TIM-1) coupled with fluorescence spectroscopy and molecular rotors to evaluate carbohydrate digestion and in vitro gastric viscosity as a function of time. A proportional relationship between total bioaccessible sugars and the concentration of available carbohydrates was observed for the different oat-based foods. The rate of starch digestion was greatest for instant oats and lowest for steel cut oats. β-glucan, starch, and total carbohydrate concentrations were proportional to the initial gastric viscosity. Overall, gastric viscosity differed considerably between samples. Instant oat and oat bran viscosities were highest at the onset of digestion and decreased with time, whereas the viscosity of steel cut oats at the onset of digestion was the lowest viscosity observed, increasing with time. These findings suggest that modification of food form and formulation during processing alters sugar bioaccessibility and luminal viscosity.

Avenanthramides (AVNs) are a family of nitrogen-containing phenolic compounds produced in oat; AVN 2c, 2p, and 2f are the three major members. An LC-MS/MS method was developed, with the limit of detection (LOD) and the limit of quantitation (LOQ) being, respectively, 0.29ng/mL and 1.96ng/mL for AVN 2c, 0.24ng/mL and 0.60ng/mL for AVE 2p, and 0.42ng/mL and 2.2ng/mL for AVN 2f. The method was validated in oat-containing hot cereal and snack bar samples. The recovery of AVN 2c, 2p, and 2f from these two oat products was 95-113%, and the relative standard deviations ranged from 5% to 9%. This method was used to evaluate oat products and raw oat samples. The effects of location and variety on AVN composition were investigated. The method presented here provides a novel and rapid tool to quantitate the abundance of AVN 2c, 2p, and 2f in oat-containing products.

This study compared the effect of a snack with ingredients to slow carbohydrate digestion (Test-snack) on postprandial blood glucose and insulin concentrations and subjective appetite ratings. We hypothesized that Test-snack would lower glucose and insulin responses and reduce appetite compared with a Control-snack. Overweight or obese subjects (n = 17) completed a randomized crossover study. Glucose, insulin, and appetite ratings were measured before consuming each snack or white bread (Bread) and over a period of 4 h. Subjects received Test-snack, Control-snack, or Bread in random order at least a week apart. The a priori primary outcome was the glucose response, and the secondary outcomes were appetite ratings and insulin responses. Mixed effects statistical models were used to perform analysis of variance in terms of the area under curve (AUC) and at specific time points. The 2-h AUC for glucose was significantly lower with Test-snack compared to Control-snack and Bread (AUC and 95% confidence intervals: Test = 2186.43 [1783.36–2589.51]; Control = 3293.75 [2893.97–3693.54]; Bread = 2800.28 [2405.79–3194.77] mg/dL · min). Four-hour AUC for glucose, and insulin, followed a similar pattern except that Test-snack did not differ from Bread. The glucose concentrations peaked at 45 min under all three conditions, but Test-snack elicited a lower response than Control-snack and Bread (P

Background The viscosity of oat β-glucan (OBG) determines its effect on serum cholesterol and glycemic responses, but whether OBG viscosity affects gastric emptying, appetite, and ad libitum food intake is unknown. Objectives We aimed to determine the effect of altering the amount or molecular weight (MW) and, hence, viscosity of OBG in a breakfast meal on the primary endpoint of food intake at a subsequent meal. Methods Overnight-fasted males (n = 16) and nonpregnant females (n = 12) without diabetes, aged 18-60 y, with BMI 20.0-30.0 kg/m² who were unrestrained eaters participated in a double-blind, randomized, crossover study at a contract research organization. Participants consumed, in random order, breakfast meals equivalent in weight, energy, and macronutrients consisting of white-bread, butter, jam, and 2% milk plus hot cereal [Cream of Rice (CR), or instant-oatmeal plus either 3 g oat-bran (2gOBG), 10 g oat-bran (4gOBG), or 10 g oat-bran plus β-glucanase (4gloMW) to reduce OBG MW and viscosity compared with 4gOBG]. Gastric emptying, subjective appetite, and glucose, insulin, ghrelin, and peptide tyrosine tyrosine (PYY) responses were assessed for 3 h and then subjects were offered an ad libitum lunch (water and pizza). Results Pizza intakes (n = 28) after CR, 2gOBG, 4gOBG, and 4gloMW (mean ± SEM: 887 ± 64, 831 ± 61, 834 ± 78, and 847 ± 68 kcal, respectively) were similar (nonsignificant). Compared with CR, 4gOBG significantly reduced glucose (78 ± 10 compared with 135 ± 15 mmol × min/L) and insulin (14.0 ± 1.6 compared with 26.8 ± 3.5 nmol × min/L) incremental area-under-the-curve and delayed gastric-emptying half-time (geometric mean: 285; 95% CI: 184, 442, compared with geometric mean: 105; 95% CI: 95, 117 min), effects not seen after 4gloMW. Subjective appetite, PYY, and ghrelin responses after 2gOBG, 4gOBG, and 4gloMW were similar to those after CR. Conclusions The results demonstrate that OBG viscosity determines its effect on postprandial glucose, insulin, and gastric emptying. However, we were unable to demonstrate a significant effect of OBG on appetite or food intake, regardless of its viscosity.This trial was registered at clinicaltrials.gov as NCT03490851.

Oats can be processed in a variety of ways ranging from minimally processed such as steel-cut oats (SCO), to mildly processed such as large-flake oats (old fashioned oats, OFO), moderately processed such as instant oats (IO) or highly processed in ready-to-eat oat cereals such as Honey Nut Cheerios (HNC). Although processing is believed to increase glycaemic and insulinaemic responses, the effect of oat processing in these respects is unclear. Thus, we compared the glycaemic and insulinaemic responses elicited by 628 kJ portions of SCO, OFO, IO and HNC and a portion of Cream of Rice cereal (CR) containing the same amount of available-carbohydrate (23 g) as the oatmeals. Healthy males (n 18) and females (n 12) completed this randomised, cross-over trial. Blood was taken fasting and at intervals for 3 h following test-meal consumption. Glucose and insulin peak-rises and incremental AUC (iAUC) were subjected to repeated-measures ANOVA using Tukey’s test (two-sided Psem) mmol/l) after OFO, 2·19 (sem 0·11), was significantly less than after CR, 2·61 (sem 0·13); and glucose peak-rise after SCO, 1·93 (sem 0·13), was significantly less than after CR, HNC, 2·49 (sem 0·13) and IO 2·47 (sem 0·13). Glucose iAUC was significantly lower after SCO than CR and HNC. Insulin peak rise was similar among the test meals, but insulin iAUC was significantly less after SCO than IO. Thus, the results show that oat processing affects glycaemic and insulinaemic responses with lower responses associated with less processing.

Background. Avenanthramides (AVA) are a group of diphenolic acids found only in oats that have anti-inflammatory and antioxidant effects. Absorption of AVAs in humans after oral consumption of natural oat flour is unknown.Objective. To examine the appearance of AVAs in plasma after oral ingestion of oat cookies and estimate key pharmacokinetic parameters.Methods. Male and female nonobese participants (n=16) consumed three cookies made with oat flour containing high (229.6 mg/kg, H-AVA) or low (32.7 mg/kg, L-AVA) amounts of AVAs, including AVA-A, AVA-B, and AVA-C. Blood samples were collected at 0, 0.5, 1, 2, 3, 5, and 10 h after ingestion. Plasma total (conjugated and free) AVA concentrations were quantified using UPLC-MS, and pharmacokinetic parameters for each AVA were estimated.Results. AVAs reached peak concentrations in plasma between 2 and 3 h for the H-AVA group and between 1 and 2 h for the L-AVA group. Maximal plasma concentrations for AVAs were higher in the H-AVA than in the L-AVA group. AVA-B demonstrated a longer half-life and slower elimination rate than AVA-A and AVA-C.Conclusions. AVAs found naturally in oats are absorbed in the plasma after oral administration in humans. AVA-B has the slowest elimination rate and the longest half-life compared to AVA-A and AVA-C, while AVA-C demonstrated the lowest plasma concentrations. This study is registered with ClinicalTrials.gov identifierNCT02415374.

OBJECTIVES: Wholegrain consumption is linked to a lower risk of cardiovascular disease. Evidence have established that the consumption of wholegrain oats lowers blood cholesterol, via a mechanism partly mediated by β-glucan. However, oats contain an array of phenolics, including ferulic acid and avenanthramides, which may also contribute to the cardiovascular health benefits. We investigated whether daily consumption of oat phenolics leads to improvement of markers of CVDrisks in adults. METHODS: In a 3 arm crossover double-blind, placebo-controlled trial, 28 volunteers consumed either: 1) oatmeal/oatcake intervention (68.1 mg of phenolics); 2) oatbran concentrate + rice porridge/wheat cracker (38.9 mg of phenolics) or 3) rice porridge/wheat cracker (13.8 mg of phenolic acids) for 4 weeks. All treatments were matched in macro nutrients, energy (500 kcal) and total soluble fiber (4.8 g). The primary endpoint was flow mediated dilatation (FMD) and other cardiovascular endpoints were laser doppler imaging, 24 h blood pressure and LDL/HDL cholesterol. RESULTS: Consumption of high phenolic oats led to a significant improvement in 24-hour SBP (−1.16 mm Hg), night time SBP (−5.1 mm Hg) and night time DBP (−2.3 mm Hg) (P

Background Slowly digested carbohydrates are perceived as beneficial by some consumers, and various regulatory bodies have published specific criteria defining lower postprandial glycemic response. We developed an optimized savory cluster snack containing slowly digested starch. Objective We compared the glucose and insulin responses elicited by the optimized (test-) cluster, a control-cluster, and an available-carbohydrate-matched portion of white bread in healthy individuals. The primary outcome was blood-glucose peak rise. We tested healthy individuals (n = 25) on 3 occasions using a randomized crossover design. On each occasion, the participants provided fasting blood samples and then consumed 1 serving of test-cluster, control-cluster, or white bread. We then measured the participants’ blood-glucose and serum-insulin concentrations over the next 4 h. Results The test-cluster elicited a significantly lower blood-glucose peak rise (mean ± SEM: 1.24 ± 0.09 mmol/L) and incremental area under the curve (iAUC; 67 ± 8 mmol × min/L) than the control-cluster (2.27 ± 0.13 mmol/L and 117 ± 10 mmol × min/L, respectively) and white bread (2.27 ± 0.16 mmol/L and 114 ± 9 mmol × min/L, respectively). The serum-insulin peak rise and iAUC elicited by the test-cluster (128 ± 13 pmol/L and 6.10 ± 0.73 nmol × min/L, respectively) and white bread (141 ± 20 pmol/L and 6.47 ± 1.11 nmol × min/L, respectively) were significantly lower than those elicited by the control-cluster (205 ± 26 pmol/L and 9.60 ± 1.31 nmol × min/L, respectively). Conclusion The test-cluster elicited lower glucose and insulin responses than the control-cluster. The results support the hypothesis that the carbohydrates in the test-cluster are digested and absorbed slowly in vivo.

Power ultrasound as an emerging processing technology has been investigated for stimulating seeds to enhance germination and accumulation of health-promoting metabolites, such as γ-aminobutyric acid (GABA) and phenolic compounds. This work was undertaken to evaluate the effects of power ultrasound (25 kHz) on the nutritional properties of germinated oats, and the microstructure of oat groats after treatment. The changes in the external and internal microstructures of the ultrasound-treated oats kernel were investigated using Environmental Scanning Electron Microscopy (ESEM) and 3D X-ray Micro Computed Tomography (Micro-CT). Physicochemical properties of oats including GABA, free sugars, avenanthramides, total phenolic content, and antioxidant capacities were enhanced after germination. Furthermore, the power ultrasound treatment for 5 min after soaking significantly enhanced the GABA (48–96 h), alanine (24–96 h), succinic acid (48–72 h), total phenolic content (24 h), and total avenanthramides (24 h) in the germinated oats.

Viscosity generated by oat β-glucan induces gastrointestinal mechanisms that influence appetite. Two oat-based ready-to-eat cereals (RTEC) with similar amounts of β-glucan but differing in their protein and sugar content were compared for their effects on appetite. Forty-seven healthy individuals, ≥18 years old, enrolled in a crossover trial consumed RTEC1 or RTEC2 in random order at least a week apart. Breakfasts contained 250kcals cereal and 105kcals fat-free milk. Subjective ratings of appetite were completed at baseline, and at 30, 60, 120, 180 and 240 minutes after consumption of the breakfast meals. Responses were analyzed as area under the curve (AUC) and per time-point. Significance was set at α=0.05. Fullness (p=0.01) and stomach fullness (p=0.02) were greater with RTEC 1 compared to RTEC 2 at 240 minutes. Stomach fullness (p=0.01) was greater at 30 minutes, and desire to eat (p=0.04) was reduced at 120 minutes with RTEC2 compared to RTEC1. There was no difference in the AUC for hunger, fullness, stomach fullness, desire to eat, or prospective intake. Ready-to-eat cereals containing similar amounts of oat β-glucan differed in the timing of significant differences in fullness or desire to eat, but appetite ratings over a four hour period did not differ.

Background/Objectives Soaking oats overnight in milk renders them ready to eat the next morning, however, it is unknown whether oats prepared this way will retain its relatively low glycaemic and insulinaemic impact. Therefore, we compared the glycaemic, insulinaemic and subjective hunger responses elicited by oats soaked overnight in 110 g skim-milk (ONO) vs. cooked cream of rice cereal (CR), both with and without inclusions. Subjects/Methods The project was performed at two research centers (Toronto, Winnipeg) as two separate studies each using a randomized, cross-over design with similar methods. The glycaemic and insulinaemic responses of overnight-fasted participants without diabetes (males:females: Toronto, 24:16; Winnipeg, 20:20) were measured for 3 h after consuming CR and ONO fed alone (Toronto) or with added sugar, nuts, and seeds (CRsns and ONOsns) (Winnipeg). Participants rated subjective hunger using visual analog scales. Data were analyzed by paired t-test. The primary endpoint was 0–2 h incremental area under the curve (iAUC) for glucose. Results Mean glucose iAUC was 33% less, after ONO than CR (mean difference was 39 (51–27) mmol × min/l, p

The objective was to investigate avenanthramides’ (AVA 2c, 2p, 2f) antioxidant molecular mechanism by examining their ability to activate Nrf2 nuclear translocation leading to the upregulation of phase II detoxification enzymes. Western blot analysis was used to access time-dependent and dose-dependent effects of AVAs on Nrf2 and heme oxygenase-1 (HO-1) expressions. The role of reactive oxygen species (ROS) in the signaling pathway was identified. To determine whether the functional α,β-unsaturated carbonyl group of AVAs plays an important role, cells were treated with dihydro-AVAs. All three AVAs significantly upregulated nuclear Nrf2 and HO-1 expressions in a time-dependent manner, with the dose-dependent effects demonstrated by 2c. The addition of NAC suppressed the HO-1 expression induced by AVAs, establishing that ROS likely plays a role on the upregulation of HO-1 by AVAs. Hydrogenation of the double bond of the functional α,β-unsaturated carbonyl group of AVAs eliminated their effects on HO-1 expression, suggesting a critical role for the functional α,β-unsaturated carbonyl group in the mechanism of action of AVAs. These results suggest AVAs induce the Keap1/Nrf2 signaling pathway in HK-2 cells, leading to the upregulation of the HO-1 phase II detoxification enzyme, potentially identifying the molecular mechanism by which AVAs exert their antioxidant effect.

Background: Appetite regulating properties of foods are usually investigated under laboratory conditions, whereas in real life, foods are consumed under at home conditions. The objective of this study was to compare the acute effects of breakfasts when tested in a laboratory condition and in an at home condition. Appetite regulating properties of two bread breakfasts and two cereal breakfasts were also compared. Subjects and methods: In this randomized cross-over trial balanced for laboratory and at home test conditions, thirty-two women consumed five breakfasts, i.e. two bread breakfasts, two cereal breakfasts and one fried-egg breakfast. Visual analogue scales for measuring appetite were captured via an on-line scoring system and were analyzed as incremental area under the curve, as satiation phase and as satiety phase. Results: Location effects were limited to two small effects only. An overall location effect in hunger feelings was observed (p = 0.040), which occurred specifically during the short satiation period (p = 0.0002) where hunger feelings scored higher under laboratory conditions. Similarly, a location effect was observed for desire to eat (p = 0.001); this was again higher under laboratory conditions. No other location effects were observed. Bread breakfasts did not differ in their appetite regulating properties. The Steel Cut oatmeal breakfast was reported to be more satiating (p = 0.001) as compared to the ready-to-eat cereal. Conclusions: Whereas the five breakfasts varied somewhat in their appetite regulating properties, evaluation under laboratory conditions overall did not result in different appetite scores compared to the at home conditions. This suggests that at home testing may be a useful alternative to laboratory test conditions for nutrition research. © 2018 Elsevier Inc.

The objectives were to assess the potential of dietary flavonoids apigenin (Api) and luteolin (Lut) to enhance the anti-proliferative effects of chemotherapeutic drugs on BxPC-3 human pancreatic cancer cells and to investigate the potential molecular mechanism of action. Simultaneous treatment or pretreatment (0, 6, 24 and 42 h) of flavonoids and chemotherapeutic drugs at various concentrations (0-50 μM) were assessed using the MTS cell proliferation assay. Simultaneous treatment with either flavonoid (13, 25 or 50 μM) and chemotherapeutic drugs 5-fluorouracil (5-FU, 50 μM) or gemcitabine (Gem, 10 μM) for 60 h resulted in mostly less-than-additive effects (p

Pancreatic cancer is the fourth leading cause of cancer mortality among both men and women in the United States with a 5-year survival rate of only 4%. Several dietary factors may influence the risk of developing pancreatic cancer and its recurrence. Some of these factors may offer innovative therapies for prevention of this disease. The goal of this review is to provide an overview of pancreatic cancer, as well as current knowledge on the epidemiological, in vitro, in vivo, and clinical studies conducted about this disease using various dietary agents. The main focus is on food-based approaches for preventing this disease particularly, citrus fruits, and foods containing flavonoids, curcumin, folate and vitamin D.

Laboratory and human studies have shown that avenanthramides (AVAs), unique compounds found in oats, are strong antioxidants. However, their specific mechanism of action remains unclear. The objective was to investigate the abilities of the three major AVAs in oats (2c, 2p, 2f) to activate Nrf2 nuclear translocation leading to the activation of phase II detoxification genes in vitro. The three AVAs significantly increased heme oxygenase-1 (HO-1) expression in HK-2 cells in both a dose- and time-dependent manner. Mechanistic studies show that HO-1 expression induced by AVAs is mediated via Nrf2 translocation. All three AVAs stimulated Nrf2 nuclear translocation in both a dose- and time-dependent manner. The addition of N-acetylcysteine (NAC) suppressed the HO-1 expression induced by 2c, 2f, and 2p, establishing that ROS plays a role on the up-regulation of HO-1 by AVAs. Pretreatment of cells with inhibitors of p38, PI3K, and MEK1 did not attenuate AVA-induced HO-1 expression, suggesting that HO-1 expressio...

Objective This study aimed to evaluate the ability of luteolin (Lut), gemcitabine (Gem), and their combination (Lut + Gem) to prevent the growth of pancreatic tumors in vivo. Methods The antitumor effect of intraperitoneally administered Lut, Gem, and Lut + Gem was evaluated using an orthotopic mouse model for 6 weeks. Tumor growth after injection of human pancreatic cancer cells was assessed by measuring pancreatic tumor mass. The mechanism of action of antitumor effect was assessed by immunohistochemistry and Western blot procedures. Results Luteolin + Gem significantly lowered (P = 0.048) the pancreatic tumor mass compared with control. Luteolin, Gem, and Lut + Gem significantly reduced the proliferating cell nuclear antigen expression (25%, 37%, and 37%, respectively). Luteolin + Gem treatment led to a significant reduction in the expressions of K-ras (46%, P = 0.0006), GSK-3β (34%, P = 0.014), P(Tyr216)GSK-3β (16%, P = 0.033), P(Ser311)NF-κB p65 (27%, P = 0.036), and bcl-2/bax ratio (68%, P = 0.006) while significantly increasing the expressions of cytochrome c (44%, P = 0.035) and caspase 3 (417%, P = 0.003). Conclusions Luteolin + Gem promoted apoptotic cell death in pancreatic tumor cells in vivo through inhibition of the K-ras/GSK-3β/NF-κB signaling pathway, leading to a reduction in the Bcl-2/Bax ratio, release of cytochrome c, and activation of caspase 3.

cope The objective was to examine the inhibitory effects of citrus fruit bioactive compounds on BxPC-3 and PANC-1 human pancreatic cancer cells, focusing on the antiproliferative mechanism of action of the flavonoid apigenin related to the glycogen synthase kinase-3β/nuclear factor kappa B signaling pathway. Methods and results Flavonoids, limonoids, phenolic acids, and ascorbic acid were tested for cytotoxic effects on BxPC-3 and PANC-1 cells; apigenin was the most potent (IC50 = 23 and 12 μM for 24 and 48 h for BxPC-3 and IC50 = 71 and 41 μM for 24 and 48 h for PANC-1). Apigenin induced pancreatic cell death through inhibition of the glycogen synthase kinase-3β/nuclear factor kappa B signaling pathway. Apigenin arrested cell cycle at G2/M phase (36 and 32% at 50 μM for BxPC-3 and PANC-1, respectively) with concomitant decrease in the expression of cyclin B1. Apigenin activated the mitochondrial pathway of apoptosis (44 and 14% at 50 μM for BxPC-3 and PANC-1, respectively) and modified the expression of apoptotic proteins. Apigenin highly upregulated the expression of cytokine genes IL17F (114.2-fold), LTA (33.1-fold), IL17C (23.2-fold), IL17A (11.3-fold), and IFNB1 (8.9-fold) in BxPC-3 cells, which potentially contributed to the anticancer properties. Conclusion Flavonoids have a protective role in pancreatic cancer tumorigenesis.

Glycogen synthase kinase-3β (GSK-3β) inhibition contributes to decreased pancreatic cancer cell proliferation and survival. The objective was to investigate the inhibitory effects of citrus compoun...

Wholegrain consumption is linked to a lower risk of cardiovascular disease. Evidence from randomized controlled trials have established that the consumption of wholegrain oats lowers blood cholesterol, via a mechanism partly mediated by β-glucan soluble fiber. However, oats contain an array of phenolic acids, including ferulic acid and also structurally related avenanthramides, which may also contribute to the cardiovascular health benefits of oat intake. We investigated whether 4 weeks, daily consumption of oat phenolics leads to improvement in markers of CVD risk men and women.In a 3 arm crossover single-blind, placebo-controlled trial, 28 volunteers consumed either: 1) oatmeal/oatcake intervention (-containing 48.9 mg of phenolic acids and 19.2 mg of avenanthramides); 2) oatbran concentrate + rice porridge/wheat cracker intervention (-containing 38.4 mg of phenolic acids and 0.5 mg of avenanthramides) or 3) rice porridge/wheat cracker intervention (containing 13.8 mg of phenolic acids). All treatments were matched in soluble fiber (4.8g) and energy (500kcal). The primary endpoint was FMD and other cardiovascular endpoints were blood pressure, LDI, LDL/HDL cholesterol, platelets and endothelial cell-derived extracellular vesicles (EVs). All measures were taken at baseline and after three, 4 week long intervention periods and two washout periods.Our data indicates an increase by 1.09 % ± 0.41 %(Mean ± SEM) in FMD response following high phenolic oat intake with a significant difference (P = 0.007) between baseline and post-intervention. Consumption of high phenolic oats also led to a significant improvement in 24-hour SBP, day time SBP and night time SBP (P < 0.01, P < 0.01 and P < 0.05) and day time and night time DBP (p < 0.05). There was also a significant decrease with total and LDL cholesterol after the consumption of moderate and high phenolic oat interventions (P < 0.05) and a small improvement in LDI (both Ach and SNP) but not significant. The number of resting endothelial EVs were also found to be increasing after the consumption of high phenolic oats.The findings of this study may provide evidence about the role of oat phenolic acids and avenanthramides in cardiovascular health and contribute to more effective public health advice about the consumption of oats and healthy cardiovascular aging.