Grape Polyphenols May Prevent High-Fat Diet-Induced Dampening of the Hypothalamic-Pituitary-Adrenal Axis in Male Mice.

Context : Chronic high-fat diet (HFD) consumption causes obesity associated with retention of bile acids (BAs) that suppress important regulatory axes, such as the hypothalamic-pituitary-adrenal axis (HPAA). HFD impairs nutrient sensing and energy balance due to a dampening of the HPAA and reduced production and peripheral metabolism of corticosterone (CORT). Objective: We assessed whether proanthocyanidin-rich grape polyphenol (GP) extract can prevent HFD-induced energy imbalance and HPAA dysregulation. Methods: Male C57BL6/J mice were fed HFD or HFD supplemented with 0.5% w/w GPs (HFD-GP) for 17 weeks. Results: GP supplementation reduced body weight gain and liver fat while increasing circadian rhythms of energy expenditure and HPAA-regulating hormones, CORT, leptin, and PYY. GP-induced improvements were accompanied by reduced mRNA levels of Il6, Il1b, and Tnfa in ileal or hepatic tissues and lower cecal abundance of Firmicutes, including known BA metabolizers. GP-supplemented mice had lower concentrations of circulating BAs, including hydrophobic and HPAA-inhibiting BAs, but higher cecal levels of taurine-conjugated BAs antagonistic to farnesoid X receptor (FXR). Compared with HFD-fed mice, GP-supplemented mice had increased mRNA levels of hepatic Cyp7a1 and Cyp27a1, suggesting reduced FXR activation and more BA synthesis. GP-supplemented mice also had reduced hepatic Abcc3 and ileal Ibabp and Ostß, indicative of less BA transfer into enterocytes and circulation. Relative to HFD-fed mice, CORT and BA metabolizing enzymes (Akr1d1 and Srd5a1) were increased, and Hsd11b1 was decreased in GP supplemented mice. Conclusion: GPs may attenuate HFD-induced weight gain by improving hormonal control of the HPAA and inducing a BA profile with less cytotoxicity and HPAA inhibition, but greater FXR antagonism.

Cellular Antioxidant Effect of an Aronia Extract and Its Polyphenolic Fractions Enriched in Proanthocyanidins, Phenolic Acids, and Anthocyanins.

Oxidative stress and chronic inflammation contribute to some chronic diseases. Aronia berries are rich in polyphenols. The aim of the present study was to characterize the cellular antioxidant effect of an aronia extract to reflect the potential physiological in vivo effect. Cellular in vitro assays in three cell lines (Caco-2, HepG2, and SH-SY5Y) were used to measure the antioxidant effect of AE, in three enriched polyphenolic fractions (A1: anthocyanins and phenolic acids; A2: oligomeric proanthocyanidins; A3: polymeric proanthocyanidins), pure polyphenols and microbial metabolites. Both direct (intracellular and membrane radical scavenging, catalase-like effect) and indirect (NRF2/ARE) antioxidant effects were assessed. AE exerted an intracellular free radical scavenging activity in the three cell lines, and A2 and A3 fractions showed a higher effect in HepG2 and Caco-2 cells. AE also exhibited a catalase-like activity, with the A3 fraction having a significant higher activity. Only A1 fraction activated the NRF2/ARE pathway. Quercetin and caffeic acid are the most potent antioxidant polyphenols, whereas cyanidin and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone showed the highest antioxidant effect among polyphenol metabolites. AE rich in polyphenols possesses broad cellular antioxidant effects, and proanthocyanidins are major contributors. Polyphenol metabolites may contribute to the overall antioxidant effect of such extract in vivo.

Phenolic Compounds Promote Diversity of Gut Microbiota and Maintain Colonic Health.

The role of non-energy-yielding nutrients on health has been meticulously studied, and the evidence shows that a compound can exert significant effects on health even if not strictly required by the organism. Phenolic compounds are among the most widely studied molecules that fit this description; they are found in plants as secondary metabolites and are not required by humans for growth or development, but they can influence a wide array of processes that modulate health across multiple organs and systems. The lower gastrointestinal tract is a prime site of action of phenolic compounds, namely, by their effects on gut microbiota and colonic health. As with humans, phenolic compounds are not required by most bacteria but can be substrates of others; in fact, some phenolic compounds exert antibacterial actions. A diet rich in phenolic compounds can lead to qualitative and quantitative effects on gut microbiota, thereby inducing indirect health effects in mammals through the action of these microorganisms. Moreover, phenolic compounds may be fermented by the gut microbiota, thereby modulating the compounds bioactivity. In the colon, phenolic compounds promote anti-inflammatory, anti-oxidant and antiproliferative actions. The aim of the present review is to highlight the role of phenolic compounds on maintaining or restoring a healthy microbiota and overall colonic health. Mechanisms of action that substantiate the reported evidence will also be discussed.

Polyphenol-induced improvements in glucose metabolism are associated with bile acid signaling to intestinal farnesoid X receptor.

INTRODUCTION: Bile acid (BA) biotransformation by gut bacteria impacts BA profile and signaling to nuclear receptors, such as the farnesoid X receptor (FXR) regulating glucose metabolism. Altered BA-FXR signaling was therefore investigated as a potential mechanism linking polyphenol-induced gut bacterial changes and improved glucose metabolism. RESEARCH DESIGN AND METHODS: Diabetic db/db were fed low-fat diet (LFD) or LFD supplemented with a proanthocyanidin-rich extract of grape polyphenols (LFD-GP) for 4 weeks. Metabolic phenotypes, serum BAs, gut microbiota composition, and gene expression markers relevant to gut barrier and glucose metabolism were assessed. Gut organoids were used to investigate effects of individual BAs on ileal FXR activity. RESULTS: Compared with LFD-fed controls, GP supplemented db/db mice showed improved glucose metabolism, decreased relative abundance of gut bacteria associated with production of secondary BAs (SBAs), and depleted serum levels of SBAs taurohyodeoxycholic acid (THDCA), ω-muricholic acid (ωMCA), and tauro-ω-muricholic acid (TωMCA). Serum levels of primary BAs (PBAs) increased, consistent with higher gene expression of PBA synthesis enzyme Cyp7a1. GP-induced BA changes associated with FXR inhibition as evidenced by reduced expression of FXR-responsive genes Shp, Fgf15, and Fabp6 in ileum tissue as well as hepatic Shp, which negatively regulates PBA synthesis. GP treatment did not affect expression of hepatic Fxr or expression of Abcb11, Slc51b, and Obp2a genes controlling BA transport. Ceramide biosynthesis genes Smpd3, Sptlc2, and Cers4 were decreased in liver and intestine suggesting lower tissue ceramides levels may contribute to improved glucose metabolism. THDCA, ωMCA, and TωMCA behaved as FXR agonists in ileal organoid experiments; therefore, their depletion in serum of GP-supplemented db/db and wild type (WT) mice was consistent with FXR inhibition. CONCLUSION: These data suggest that by altering the gut microbiota, GPs modify BA-FXR signaling pathways to promote glucoregulation.

Inhibition of intestinal glucose transport by polyphenols: a mechanism for indirect attenuation of cholesterol absorption?

Cholesterol uptake and chylomicron synthesis are promoted by increasing glucose concentrations in both healthy and diabetic individuals during the postprandial phase. The goal of this study was to test whether acute inhibition of glucose uptake could impact cholesterol absorption in differentiated human intestinal Caco-2 cells. As expected, high glucose upregulated intestinal cholesterol metabolism promoting its uptake and incorporation in lipoproteins. This was accompanied by an increase in the gene expression of Niemann-Pick C1 Like 1 and proprotein convertase subtillisin/kexin type 9. Cholesterol uptake was attenuated by acute inhibition of glucose absorption by cytochalasin B, by a chamomile extract and by one of its main constituent polyphenols, apigenin 7-O-glucoside; however, chylomicron secretion was only reduced by the chamomile extract. These data support a potential indirect role for bioactives in modulating intestinal lipid pathways through effects on intestinal glucose uptake. This working hypothesis warrants further testing in an in vivo setting such as in hypercholesterolaemic or prediabetic individuals.

The Gastrointestinal Tract as Prime Site for Cardiometabolic Protection by Dietary Polyphenols.

Substantial evidence from nutritional epidemiology links polyphenol-rich diets with reduced incidence of chronic disorders; however, biological mechanisms underlying polyphenol-disease relations remain enigmatic. Emerging evidence is beginning to unmask the contribution of the gastrointestinal tract on whole-body energy homeostasis, suggesting that the intestine may be a prime target for intervention and a fundamental site for the metabolic actions of polyphenols. During their transit through the gastrointestinal tract, polyphenols may activate enteric nutrient sensors ensuing appropriate responses from other peripheral organs to regulate metabolic homeostasis. Furthermore, polyphenols can modulate the absorption of glucose, attenuating exaggerated hormonal responses and metabolic imbalances. Polyphenols that escape absorption are metabolized by the gut microbiota and the resulting catabolites may act locally, activating nuclear receptors that control enteric functions such as intestinal permeability. Finally, polyphenols modulate gut microbial ecology, which can have profound effects on cardiometabolic health.

The effect of ageing temperature on the physicochemical properties, phytochemical profile and α-glucosidase inhibition of Hibiscus sabdariffa (roselle) wine.

The effect of temperature (6, 15 and 30°C) during ageing on the colour, phytochemical composition and bioactivity of roselle wine was investigated over 12months. At the end of ageing, wines stored at 6°C had the highest colour density and lowest polymeric anthocyanins. The initial concentration of most of the individual phenolic compounds decreased during ageing, with reduction of monomeric anthocyanins contributing to the formation of anthocyanin-derivatives (pyranoanthocyanins), eight of which were identified tentatively and reported here for the first time in roselle wine. The decrease in individual phenolic compounds did not affect inhibition of α-glucosidase (maltase) activity, which remained relatively low but stable throughout ageing. Diethyl succinate was the only volatile clearly influenced by ageing temperature, with the most pronounced effect at 30°C (∼256 fold increase). In summary, the final concentrations of anthocyanins and diethyl succinate were the major compounds influenced by ageing temperature.

Acute metabolic actions of the major polyphenols in chamomile: an in vitro mechanistic study on their potential to attenuate postprandial hyperglycaemia.

Transient hyperglycaemia is a risk factor for type 2 diabetes and endothelial dysfunction, especially in subjects with impaired glucose tolerance. Nutritional interventions and strategies for controlling postprandial overshoot of blood sugars are considered key in preventing progress to the disease state. We have identified apigenin-7-O-glucoside, apigenin, and (Z) and (E)-2-hydroxy-4-methoxycinnamic acid glucosides as the active (poly)phenols in Chamomile (Matricaria recutita) able to modulate carbohydrate digestion and absorption in vitro as assessed by inhibition of α-amylase and maltase activities. The latter two compounds previously mistakenly identified as ferulic acid hexosides were purified and characterised and studied for their contribution to the overall bioactivity of chamomile. Molecular docking studies revealed that apigenin and cinnamic acids present totally different poses in the active site of human α-amylase. In differentiated Caco-2/TC7 cell monolayers, apigenin-7-O-glucoside and apigenin strongly inhibited D-[U-14C]-glucose and D-[U-14C]-sucrose transport, and less effectively D-[U-14C]-fructose transport. Inhibition of D-[U-14C]-glucose transport by apigenin was stronger under Na+-depleted conditions, suggesting interaction with the GLUT2 transporter. Competitive binding studies with molecular probes indicate apigenin interacts primarily at the exofacial-binding site of GLUT2. Taken together, the individual components of Chamomile are promising agents for regulating carbohydrate digestion and sugar absorption at the site of the gastrointestinal tract.

Green and Chamomile Teas, but not Acarbose, Attenuate Glucose and Fructose Transport via Inhibition of GLUT2 and GLUT5.

SCOPE: High glycaemic sugars result in blood-glucose spikes, while large doses of post-prandial fructose inundate the liver, causing an imbalance in energy metabolism, both leading to increased risk of metabolic malfunction and type 2 diabetes. Acarbose, used for diabetes management, reduces post-prandial hyperglycaemia by delaying carbohydrate digestion. METHODS AND RESULTS: Chamomile and green teas both inhibited digestive enzymes (α-amylase and maltase) related to intestinal sugar release, as already established for acarbose. However, acarbose had no effect on uptake of sugars using both differentiated human Caco-2 cell monolayers and Xenopus oocytes expressing human glucose transporter-2 (GLUT2) and GLUT5. Both teas effectively inhibited transport of fructose and glucose through GLUT2 inhibition, while chamomile tea also inhibited GLUT5. Long term incubation of Caco-2/TC7 cells with chamomile tea for 16 h or 4 days did not enhance the observed effects, indicating that inhibition is acute. Sucrase activity was directly inhibited by green tea and acarbose, but not chamomile. CONCLUSION: These findings show that chamomile and green teas are potential tools to manage absorption and metabolism of sugars with efficacy against high sugar bolus stress inflicted, for example, by high fructose syrups, where the drug acarbose would be ineffective.

Maintaining antioxidant potential of fresh fruits and vegetables after harvest.

The consumption of fruits and vegetables has increased in the past few years, not only because of their attractive sensorial properties, but also for their nutritional and health benefits. Antioxidants are compounds found in fresh fruits and vegetables, and evidence of their role in the prevention of degenerative diseases is continuously emerging. However, the antioxidants in some fruits and vegetables can be lost during handling after harvest, even during minimal processing and storage. In this sense, postharvest treatments are needed to preserve the quality and antioxidant potential of fresh produce. Postharvest treatments and technologic strategies (including ultraviolet light, controlled and modified atmospheres, heat treatments, and application of natural compounds, such as edible coatings, active packaging, microencapsulation, and nanoemulsion) have shown positive and promising results to maintain fruit and vegetable antioxidant potential. The purpose of this review is to analyze and propose the application of postharvest strategies to maintain, or even improve, the antioxidant status of fruits and vegetables, thus offering options to maximize health benefits to consumers.

Effect of edible coatings on bioactive compounds and antioxidant capacity of tomatoes at different maturity stages.

This work evaluated the effect of carnauba and mineral oil coatings on the bioactive compounds and antioxidant capacity of tomato fruits (cv. "Grandela"). Carnauba and mineral oil coatings were applied on fresh tomatoes at two maturity stages (breaker and pink) over 28 day of storage at 10 °C was evaluated. Bioactive compound and antioxidant activity assays included total phenols, total flavonoids, ascorbic acid (ASA), lycopene, DPPH radical scavenging activity (%RSA), trolox equivalent antioxidant capacity (TEAC) and oxygen radical absorbance capacity assay (ORAC). The total phenolic, flavonoid and lycopene contents were significantly lower for coated fruit than control fruits. However, ascorbic acid content was highest in fruits treated with carnauba, followed by mineral oil coating and control fruits. The ORAC values were highest in breaker tomatoes coated with carnauba wax, followed by mineral oil-coated fruits and controls. No significant differences in ORAC values were observed in pink tomatoes. % RSA and TEAC values were higher for controls than for coated fruit. Edible coatings preserve the overall quality of tomatoes during storage without affecting the nutritional quality of fruit. We found that the physiological response to the coatings is in function of the maturity stage of tomatoes. The information obtained in this study support to use of edible coating as a safe and good alternative to preserve tomato quality, and that the changes of bioactive compounds and antioxidant activity of tomato fruits, was not negatively affected. This approach can be used by producers to preserve tomato quality.