Comparison of chemometric strategies for potential exposure marker discovery and false-positive reduction in untargeted metabolomics: application to the serum analysis by LC-HRMS after intake of Vaccinium fruit supplements.

Untargeted liquid chromatographic-high-resolution mass spectrometric (LC-HRMS) metabolomics for potential exposure marker (PEM) discovery in nutrikinetic studies generates complex outputs. The correct selection of statistically significant PEMs is a crucial analytical step for understanding nutrition-health interactions. Hence, in this paper, different chemometric selection workflows for PEM discovery, using multivariate or univariate parametric or non-parametric data analyses, were comparatively tested and evaluated. The PEM selection protocols were applied to a small-sample-size untargeted LC-HRMS study of a longitudinal set of serum samples from 20 volunteers after a single intake of (poly)phenolic-rich Vaccinium myrtillus and Vaccinium corymbosum supplements. The non-parametric Games-Howell test identified a restricted group of significant features, thus minimizing the risk of false-positive retention. Among the forty-seven PEMs exhibiting a statistically significant postprandial kinetics, twelve were successfully annotated as purine pathway metabolites, benzoic and benzodiol metabolites, indole alkaloids, and organic and fatty acids, and five (i.e. octahydro-methyl-ß-carboline-dicarboxylic acid, tetrahydro-methyl-ß-carboline-dicarboxylic acid, citric acid, caprylic acid, and azelaic acid) were associated to Vaccinium berry consumption for the first time. The analysis of the area under the curve of the longitudinal dataset highlighted thirteen statistically significant PEMs discriminating the two interventions, including four intra-intervention relevant metabolites (i.e. abscisic acid glucuronide, catechol sulphate, methyl-catechol sulphate, and α-hydroxy-hippuric acid). Principal component analysis and sample classification through linear discriminant analysis performed on PEM maximum intensity confirmed the discriminating role of these PEMs.

Screening of bioactive ingredients of Tsantan Sumtang in ameliorating H9c2 cells injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Tsantan Sumtang (TS), a traditional Tibetan medicine, has been used in the clinic for the treatment of myocardial ischemia (MI) for ages, however, the bioactive ingredients that are responsible for improving MI remain unknown. AIM OF THE STUDY: This study investigated the chemical components of TS and their medicinal efficacies at cell levels, in order to expound the bioactive ingredients in TS. MATERIALS AND METHODS: First, a response-surface methodology was employed to determine the optimum ethanol reflux extraction process of polyphenols in TS (PTS) due to their close correlation with MI improvement. Second, a serum pharmacochemistry technique was used to analyze the compounds of PTS absorbed into the blood of rats. Third, hypoxia-, H2O2-, and adriamycin (ADM)-induced H9c2 cell injury models were used to investigate the cardioprotective effects of these compounds in vitro. Fourth, protective effects of isovitexin, quercitrin, and isoeugenol on mitochondrial function were further tested. RESULTS: The optimum extraction conditions for obtaining PTS were an ethanol concentration of 78.22%, an extraction time of 67.4 min, and a material-liquid ratio of 1:72.60 mL/g. Serum pharmacochemistry analysis detected 21 compounds, of which 11 compounds were always present in the blood within 5 h. Cytotoxicity and the protective effect of 11 compounds in hypoxia-, H2O2-, and ADM-induced H9c2 cell injury models shown that isovitexin, quercitrin, and isoeugenol had almost no cytotoxicity, and they could elevate the survival rate in injured H9c2 cells. Furthermore, isovitexin, quercitrin, and isoeugenol could decrease mitochondrial reactive oxygen species (ROS) releasion, inhibite mitochondrial permeability transition pore (mPTP) opening, ameliorate the change of mitochondrial membrane potential (MMP) to exert mitochondrial protection effect. CONCLUSION: Isovitexin, quercitrin, and isoeugenol exhibited cardioprotective effect at cell levles, these three compounds might be the bioactive ingredients in TS. These findings elucidate the pharmacodynamic substances and mechanisms of TS, guiding its clinical use.

Effects of strawberries on bone biomarkers in pre- and stage 1-hypertensive postmenopausal women: a secondary analysis.

Postmenopausal women experience an increase in bone remodeling with the rate of bone resorption superseding the rate of bone formation. This results in a net bone loss with a subsequent increased risk for osteoporosis and fractures. High blood pressure (BP) has been associated with loss of bone mineral density and increased propensity to fractures. Strawberries are rich in polyphenols, which have been shown to have anti-hypertensive and bone-protective properties. Thus, we examined whether daily intake of strawberries would positively affect biomarkers of bone metabolism in postmenopausal women with pre- and stage 1-hypertension. Participants (age: 59 ± 6 years; body mass index: 31.5 ± 4.1 kg m-2; systolic BP: 140 ± 13 mmHg) were randomly assigned to consume (1) 50 g of freeze-dried strawberry powder (FDSP), (2) 25 g FDSP + 25 g of placebo powder, or (3) 50 g placebo powder for eight weeks. Results indicate a significant time-by-treatment interaction (P = 0.04) for serum insulin-like growth factor (IGF)-1, a hormone that plays a major role in bone formation. Serum concentrations of bone-specific alkaline phosphatase, a marker of bone formation, and tartrate-resistant acid phosphatase-5b, a specific marker of bone resorption, were not affected by FDSP compared to placebo. Although not statistically significant, after eight weeks, osteocalcin increased in the 50 g FDSP group with a large effect size (d = 0.6) when compared to the placebo-control group. Adiponectin increased by 5% and 6% in the 25 g and 50 g FDSP groups, respectively, while it declined in the placebo-control group by 25% (P = 0.03 for time-by-treatment interaction). Our findings suggest that consumption of 25 g FDSP increases IGF-1 in postmenopausal women with pre- and stage 1-hypertension. However, further studies are needed to assert the effectiveness of a strawberry intervention for bone health.

Overview of Beneficial Effects of (Poly)phenol Metabolites in the Context of Neurodegenerative Diseases on Model Organisms.

The rise of neurodegenerative diseases in an aging population is an increasing problem of health, social and economic consequences. Epidemiological and intervention studies have demonstrated that diets rich in (poly)phenols can have potent health benefits on cognitive decline and neurodegenerative diseases. Meanwhile, the role of gut microbiota is ever more evident in modulating the catabolism of (poly)phenols to dozens of low molecular weight (poly)phenol metabolites that have been identified in plasma and urine. These metabolites can reach circulation in higher concentrations than parent (poly)phenols and persist for longer periods of time. However, studies addressing their potential brain effects are still lacking. In this review, we will discuss different model organisms that have been used to study how low molecular weight (poly)phenol metabolites affect neuronal related mechanisms gathering critical insight on their potential to tackle the major hallmarks of neurodegeneration.

The Metabolomic-Gut-Clinical Axis of Mankai Plant-Derived Dietary Polyphenols.

BACKGROUND: Polyphenols are secondary metabolites produced by plants to defend themselves from environmental stressors. We explored the effect of Wolffia globosa 'Mankai', a novel cultivated strain of a polyphenol-rich aquatic plant, on the metabolomic-gut clinical axis in vitro, in-vivo and in a clinical trial. METHODS: We used mass-spectrometry-based metabolomics methods from three laboratories to detect Mankai phenolic metabolites and examined predicted functional pathways in a Mankai artificial-gut bioreactor. Plasma and urine polyphenols were assessed among the 294 DIRECT-PLUS 18-month trial participants, comparing the effect of a polyphenol-rich green-Mediterranean diet (+1240 mg/polyphenols/day, provided by Mankai, green tea and walnuts) to a walnuts-enriched (+440 mg/polyphenols/day) Mediterranean diet and a healthy controlled diet. RESULTS: Approximately 200 different phenolic compounds were specifically detected in the Mankai plant. The Mankai-supplemented bioreactor artificial gut displayed a significantly higher relative-abundance of 16S-rRNA bacterial gene sequences encoding for enzymes involved in phenolic compound degradation. In humans, several Mankai-related plasma and urine polyphenols were differentially elevated in the green Mediterranean group compared with the other groups (p < 0.05) after six and 18 months of intervention (e.g., urine hydroxy-phenyl-acetic-acid and urolithin-A; plasma Naringenin and 2,5-diOH-benzoic-acid). Specific polyphenols, such as urolithin-A and 4-ethylphenol, were directly involved with clinical weight-related changes. CONCLUSIONS: The Mankai new plant is rich in various unique potent polyphenols, potentially affecting the metabolomic-gut-clinical axis.

(Poly)phenol-Rich Diets in the Management of Endothelial Dysfunction in Diabetes Mellitus: Biological Properties in Cultured Endothelial Cells.

Processed and ready-to-eat foods become routinely consumed resulting in a sharp rise of sugar intake in people's daily diets. The inclusion of fresh fruits and vegetables rich in (poly)phenols has been encouraged by the World Health Organization (WHO) as part of the daily choices to ameliorate endothelial dysfunction and ease the socio-economic burden of diabetes. Research in Food, Nutrition, and Cell Metabolism areas is revealing that the health benefits of (poly)phenol-rich foods go beyond their antioxidant properties and are in fact key modulators of redox and glycaemia status, and inflammatory response contributing to improved endothelial function and vascular health in diabetes. Other beneficial aspects include appetite modulation, regulation of hydrolytic enzymes involved in sugar and lipid metabolism, and mediation of cell-cell aggregation events. This work overviews the current knowledge on the biological properties of ingested (poly)phenols in cultured endothelial cells with emphasis on the circulating (poly)phenols, providing support to (poly)phenol-rich diets as alternatives to drug-based therapies in the prevention, treatment, and management of diabetes. A critical evaluation on the caveats and challenges involve in current experimental cell-based designs and approaches adopted is also discussed.

Sweetener influences plasma concentration of flavonoids in humans after an acute intake of a new (poly)phenol-rich beverage.

BACKGROUND AND AIM: The overconsumption of sucrose is closely related to sugar-sweetened beverages and one of the main factors associated with the increase of metabolic diseases, such as type 2 diabetes, obesity, and insulin resistance. So, the addition of alternative sweeteners to new fruit-based drinks could contribute to minimizing the incidence or severity of these pathologies. Nevertheless, current knowledge on the influence of these additives on the bioactive compounds present in these beverages is still scarce.new-onset hypertension, but few data were published in Asian. We aimed to investigate the association of lipid profiles with new-onset hypertension in a Chinese community-based non-hypertensive cohort without lipid-lowering treatment (n = 1802). METHODS AND RESULTS: Hence, to contribute to the understanding of this issue, the plasma concentration of phenolic compounds (anthocyanins and flavanones), after the ingestion of a new maqui-citrus-based beverage, supplemented with sucrose (natural high caloric), stevia (natural non-caloric), or sucralose (artificial non-caloric), was evaluated as evidence of their intestinal absorption and metabolism previous to renal excretion. The beverages were ingested by volunteers (n = 20) and the resulting phenolic metabolites in plasma were analyzed by UHPLC-ESI-MS/MS. A total of 13 metabolites were detected: caffeic acid sulfate, caffeic acid glucuronide, 3,4-dihydroxyfenylacetic, 3,4-dihydroxyfenylacetic sulfate. 3,4-dihydroxyfenylacetic acid di-sulfate, 3,4-dihydroxyfenylacetic di-glucuronide, 3,4-dihydroxyfenylacetic glucuronide-sulfate, trans-ferulic acid glucuronide, naringenin glucuronide, vanillic acid, vanillic acid sulfate, vanillic acid glucuronide-sulfate, and vanillic acid di-glucuronide, being recorded their maximum concentration after 30-60 min. CONCLUSION: In general, sucralose provided the greatest absorption value for most of these metabolites, followed by stevia. Due to this, the present study proposes sucralose and stevia (non-caloric sweeteners) as valuable alternatives to sucrose (high caloric sweetener), to avoid the augmented risk of several metabolic disorders.

A Validated LC-MS/MS Method for the Simultaneous Determination of Ticagrelor, Its Two Metabolites and Major Constituents of Tea Polyphenols in Rat Plasma and Its Application in a Pharmacokinetic Study.

Ticagrelor is recommended for management of patients with acute coronary syndromes. Green tea is one of the most popular beverages in China and around the world. Their concomitant use is unavoidable. In this study, a selective and sensitive liquid chromatography-tandem mass spectrometry method for the simultaneous determination of plasma concentrations of ticagrelor, its two metabolites and four major constituents of tea polyphenols (TPs) in rats was developed for co-administration study of ticagrelor and TPs. Diazepam was used as internal standard (IS). Plasma samples were extracted employing a liquid-liquid extraction technique. Chromatographic separation was carried out on a Kinetex C18 column (2.1 × 75 mm, 2.6 µm) by gradient elution using 0.1% formic acid in water, acetonitrile and methanol. Seven analytes and IS were detected by a mass spectrometer with both positive and negative ionization by multiple reaction monitoring mode. The method was fully validated to be reliable and reproducible in accordance with food and drug administration (FDA) guidelines on bioanalytical method validation. The method was then successfully applied for pharmacokinetic study of ticagrelor, its two metabolites and four major constituents of TPs in rat plasma after oral administration of ticagrelor and tea polyphenol extracts.

Putative metabolites involved in the beneficial effects of wholegrain cereal: Nontargeted metabolite profiling approach.

BACKGROUND AND AIMS: Wholegrain cereals have been implicated in the reduction of lifestyle-related chronic diseases risk including cardiovascular diseases and type 2 diabetes. Molecular mechanisms responsible for the beneficial health effects are not entirely understood. The aims of this study were 1) to identify new potential plasma biomarker candidate metabolites of wholegrain cereal foods intake and 2) to examine whether some putative metabolites associated with wholegrain foods intake may play a role in the improvement of cardiometabolic risk factors. METHODS AND RESULTS: Analysis have been conducted in 54 individuals with metabolic syndrome of both genders, age 40-65 years, randomly assigned to 2 dietary interventions lasting 12-week: 1) wholegrain enriched diet (n = 28), and 2) refined-wheat cereals diet (control diet) (n = 26). Nontargeted metabolite profiling analysis was performed on fasting plasma samples collected at baseline and at the end of the experimental diets. Our data show that, at the end of the intervention, a higher intake of wholegrain (tertile 3) was significantly associated with a marked increase in several lipid compounds, as PC (20:4/16:1), LPC (20:4), LPC (22:6), LPC (18:3), LPC (22:5), and a phenolic compound (P < .05 for all). In the wholegrain group, higher concentrations of these metabolites (tertile 3 vs tertile 1 of each metabolite) were significantly associated with lower postprandial insulin and triglyceride responses (P < .05) by 29% and 37%, respectively. CONCLUSION: These observations suggest a possible role of lipid and polyphenol metabolites in the postprandial metabolic benefits of wholegrains in subjects at high risk of cardiovascular disease. In addition, they provide insight into the role of these metabolites as potential candidate biomarkers of wholegrain foods. The study was registered on ClinicalTrials.gov (identifier: NCT00945854).

Quantitative Assessment of Dietary (Poly)phenol Intake: A High-Throughput Targeted Metabolomics Method for Blood and Urine Samples.

Many studies have associated the consumption of (poly)phenol-rich diets with health benefits. However, accurate high-throughput quantitative methods for estimating exposure covering a broad spectrum of (poly)phenols are lacking. We have developed and validated a high-throughput method for the simultaneous quantification of 119 (poly)phenol metabolites in plasma and urine using ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry, with a very fast sample treatment and a single run time of 16 min. This method is highly sensitive, precise, accurate, and shows good linearity for all compounds (R2 > 0.992). This novel method will allow a quantitative assessment of habitual (poly)phenol intake in large epidemiological studies as well as clinical studies investigating the health benefits of dietary (poly)phenols.

Comparative pharmacokinetics of seven bioactive components in normal, sham-operated, and myocardial ischemia-reperfusion injury rats after oral administration of the Salvia Miltiorrhiza-Moutan Cortex herb pair.

Recently the Salvia Miltiorrhiza-Moutan Cortex (SM-MC) herb pair is considered as a promising Chinese medicinal mixture exhibiting a range of pharmacological activities, including treating cardiovascular disease due to its unique composition. In this study, we conducted the comparative pharmacokinetic analysis of seven main bioactive components of SM-MC in a different model rat. A straightforward ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) strategy that could simultaneously evaluate the levels of seven compounds was used to ensure the reliability of these pharmacokinetic analyses in rat plasma. The rat plasma samples were collected from normal, sham-operated, and myocardial ischemia-reperfusion injury (MIRI) groups at predetermined time points after the administration of SM-MC. The main pharmacokinetic parameters were detected and calculated. We successfully assessed the maximum concentration (Cmax ), time to Cmax (Tmax ), the elimination rate constant (λz ), total half-life (t1/2 ), total body clearance (CL), and the area under the concentration-time curve from 0 to last sampling time (AUC0-t ) and extrapolated to infinity (AUC0-∞ ). To sum up, an optimized UPLC-MS/MS approach that could be used to rapidly, simultaneously, and sensitively detect seven bioactive compounds derived from SM-MC extract preparations was successfully developed, which may offer a pharmacokinetic basis for preclinical and clinical studies of SM-MC herb pair for treating MIRI.

Pharmacokinetic Characterization of (Poly)phenolic Metabolites in Human Plasma and Urine after Acute and Short-Term Daily Consumption of Mango Pulp.

Pharmacokinetic (PK) evaluation of polyphenolic metabolites over 24 h was conducted in human subjects (n = 13, BMI = 22.7 ± 0.4 kg/m2) after acute mango pulp (MP), vitamin C (VC) or MP + VC test beverage intake and after 14 days of MP beverage intake. Plasma and urine samples were collected at different time intervals and analyzed using targeted and non-targeted mass spectrometry. The maximum concentrations (Cmax) of gallotannin metabolites were significantly increased (p < 0.05) after acute MP beverage intake compared to VC beverage alone. MP + VC beverage non-significantly enhanced the Cmax of gallic acid metabolites compared to MP beverage alone. Pyrogallol (microbial-derived metabolite) derivatives increased (3.6%) after the 14 days of MP beverage intake compared to 24 h acute MP beverage intake (p < 0.05). These results indicate extensive absorption and breakdown of gallotannins to galloyl and other (poly)phenolic metabolites after MP consumption, suggesting modulation and/or acclimation of gut microbiota to daily MP intake.

Plasma and Urinary (Poly)phenolic Profiles after 4-Week Red Raspberry (Rubus idaeus L.) Intake with or without Fructo-Oligosaccharide Supplementation.

Red raspberries (RRB) are high in anthocyanin- and ellagitannin- type (poly)phenols. This study aimed to investigate the effect of 4-week RRB supplementation on (poly)phenolic metabolism in adults with prediabetes and insulin-resistance (PreDM-IR); and whether adding fructo-oligosaccharides (FOS), prebiotics, would augment the microbial metabolites of RRB (poly)phenols. In a randomized crossover clinical trial, subjects (n = 35: PreDM-IR, n = 25; healthy Reference group, n = 10) consumed 1 cup RRB (fresh weight equivalence) per day and RRB with 8 g FOS per day each for 4 weeks in random order separated by 4-week washout. Plasma and urinary (poly)phenolic metabolites were characterized after (0-24h) consuming a RRB-based test drink (2 cups RRB) at baseline/week 0 and again after 4-week supplementations. A total of 123 (poly)phenolic metabolites were quantified. After 4-week RRB supplementation, several metabolite groups were significantly increased (p < 0.05), including urolithins, phenyl-γ-valerolactones, and phenolic acids. Supplementing FOS with RRB for 4 weeks enhanced benzoic acid derivatives compared to the baseline (p < 0.05). Specific effects of supplementation by metabolic status indicated 4-week RRB supplementation significantly increased microbial metabolites that were lower in PreDM-IR group. Our results suggest alterations in the capacity of PreDM-IR group to metabolize and render bioavailable raspberry-derived (poly)phenols when consumed regularly.

Black Soybean Improves Vascular Function and Blood Pressure: A Randomized, Placebo Controlled, Crossover Trial in Humans.

Vascular dysfunction and injurious stimuli such as oxidative stress are closely related to the risk of cardiovascular diseases (CVD). Dietary polyphenols are reported to exert beneficial effects in reducing the risk of CVD. Black soybean has been used as a nutritionally rich food and contains abundant polyphenols in its seed coat and grain. Black soybean has many beneficial physiological activities, and its prevention effects on CVD risk were reported mainly in animal experiments. In this study, we performed a randomized, single blind, placebo controlled, crossover trial to investigate the effect of black soybean consumption on the vascular function in healthy humans. Twenty-two healthy adults aged from 30 to 60 completed the four week trial with daily consumption of about a 40 g test material cookie containing 20 g roasted black soybean powder. Body composition, vascular function, biomarkers for oxidative stress, and polyphenol contents in the urine and the plasma were measured. After ingestion of the black soybean cookie, vascular function, which was evaluated by plethysmogram using a Pulse Analyzer®, was improved and systolic blood pressure was decreased. Moreover, nitric oxide levels in plasma and urine were increased, while an oxidative stress biomarker, 8-hydroxy-2'-deoxyguanosine level, in the plasma was decreased accompanied by an increase in the concentration of polyphenols derived from black soybean in plasma and urine. These results suggest that the antioxidant activity of black soybean polyphenols and an increase in the nitric oxide level may contribute to the improvement of vascular function. Thus, black soybean is an attractive food material for improvement of vascular function through decreasing oxidative stress by its potent antioxidant activity and increasing the nitric oxide level in healthy humans.

Total Dietary Antioxidant Intake Including Polyphenol Content: Is it Capable to Fight against Increased Oxidants within the Body of Ultra-Endurance Athletes?

The role of dietary antioxidants on exhaustive exercise-induced oxidative stress has been well investigated. However, the contribution of total dietary antioxidant capacity on exogenous antioxidant defense and exercise performance has commonly been disregarded. The aims of the present investigation were to examine (i) the effects of dietary total antioxidant intake on body antioxidant mechanisms, and (ii) an exhaustive exercise-induced oxidative damage in ultra-endurance athletes. The study included 24 ultra-marathon runners and long-distance triathletes (12 male and 12 female) who underwent an acute exhaustive exercise test (a cycle ergometer (45 min at 65% VO2max) immediately followed by a treadmill test (75% VO2max to exhaustion). Oxidative stress-related biomarkers (8-isoprostaglandin F2alpha (8-iso PGF2a), total oxidant status (TOS, total antioxidant status (TAS)) in plasma were collected before and after exercise. Oxidative stress index was calculated to assess the aspect of redox balance. Blood lactate concentrations and heart rate were measured at the 3rd and 6th min after exercise. Dietary antioxidant intake was calculated using the ferric reducing ability of plasma (FRAP) assay. Dietary total antioxidant intake of the subjects was negatively correlated with pre-exercise TOS concentrations (rs = -0.641 in male, and rs = -0.741 in females) and post- vs. pre- (∆) 8-iso PGF2a levels (rs = -0.702 in male; p = 0.016, and rs = -0.682 in females; p = 0.024), and positively correlated with ∆ TAS concentrations (rs = 0.893 in males; p = 0.001, and rs = 0.769 in females; p = 0.002) and post- exercise lactate concentrations (rs = 0.795 for males; p = 0.006, and rs = 0.642 for females; p = 0.024). A positive meaningful (p = 0.013) interaction was observed between time at exhaustion and dietary antioxidant intake (rs = 0.692) in males, but not in females. In conclusion, the determination of total dietary antioxidant intake in ultra-endurance athletes may be crucial for gaining a better perspective on body antioxidant defense against exhaustive exercise-induced oxidative stress. However, the effects of dietary antioxidant on exercise performance and recovery rate needs further investigation.

The Presence of Caffeic Acid in Cerebrospinal Fluid: Evidence That Dietary Polyphenols Can Cross the Blood-Brain Barrier in Humans.

Epidemiological data indicate that a diet rich in plant polyphenols has a positive effect on brain functions, improving memory and cognition in humans. Direct activity of ingested phenolics on brain neurons may be one of plausible mechanisms explaining these data. This also suggests that some phenolics can cross the blood-brain barrier and be present in the brain or cerebrospinal fluid. We measured 12 phenolics (a combination of the solid-phase extraction technique with high-performance liquid chromatography) in cerebrospinal fluid and matched plasma samples from 28 patients undergoing diagnostic lumbar puncture due to neurological disorders. Homovanillic acid, 3-hydroxyphenyl acetic acid and caffeic acid were detectable in cerebrospinal fluid reaching concentrations (median; interquartile range) 0.18; 0.14 µmol/L, 4.35; 7.36 µmol/L and 0.02; 0.01 µmol/L, respectively. Plasma concentrations of caffeic acid (0.03; 0.01 µmol/L) did not correlate with those in cerebrospinal fluid (ρ = -0.109, p = 0.58). Because food (fruits and vegetables) is the only source of caffeic acid in human body fluids, our results indicate that the same dietary phenolics can cross blood-brain barrier in humans, and that transportation of caffeic acid through this barrier is not the result of simple or facilitated diffusion.

Black soybean improves the vascular function through an increase in nitric oxide and a decrease in oxidative stress in healthy women.

Vascular dysfunction and injurious stimuli such as oxidative stress is closely related to the risk of cardiovascular diseases (CVD). Dietary polyphenols is reported to exert the beneficial effects on reducing the risk of CVD. Black soybean is rich in polyphenols, including isoflavones, anthocyanidins and flavan-3-ols, and its prevention effects on CVD risk were reported in the animal experiments. In this study, we investigated the effect of black soybean consumption on the vascular function and oxidative stress associating with the polyphenol concentrations in healthy women. Lowered vascular age was observed in 33 out of 44 volunteers who completed the 8-week trial. It was observed that improvement of the vascular stiffness, increasing in the urinary NO2 and NO3 level, and decreasing in the oxidative stress markers, 8-hydroxy-2'-deoxyguanosine, hexanoyl-lysine and myeloperoxidase. In addition, concentration of 12 polyphenols in black soybean increased in the plasma and urine. Increased concentration of polyphenols would be involved in the decreased oxidative stress. Thus, black soybean consumption improved the vascular function through an increase in nitric oxide and a decrease in oxidative stress accompanied by increasing the polyphenol concentrations in healthy women.

Optimization of the ultrasound-assisted extraction of polyphenol, mangiferin, and its antioxidant expressionin mango peel (Mangifera indica) using response surface methodology.

BACKGROUND: Emerging extraction techniques for bioactive compounds have been cataloged as efficient and cost effective compared to conventional ones. The objective of this research was to define the time and temperature that will guarantee a higher mangiferin content and antioxidant potential in Colombian Criollo mango peel through Ultrasound Assisted Extraction (UAE). METHODS: To find the optimal extraction conditions, response surface methodology was used, proposing a 32 factorial experimental design having as response variables the content of mangiferin and total phenols, and the antioxidant activity measured through ABTS and ORAC techniques. RESULTS: According to the results obtained, the R2 values were in accordance with the adjusted R2 values, showing that the data fit the model well. The results showed that both time and temperature had a significant effect on all the variables evaluated (p < 0.05). The optimization of multiple responses showed that the optimal extraction conditions were 10 min and 54°C; these values were performed experimentally to compare theoretical values, finding percentages of standard residual error of less than 5%. CONCLUSIONS: This allows the conclusion that the optimal parameters of temperature and time in ultrasound- assisted extraction were defined in Criollo mango peel. On the other hand, the peel showed a considerable metabolite content and antioxidant activity, suggesting it as a possible functional additive in the production of juices, nectars, and other mango-based products.

Combined effect of interventions with pure or enriched mixtures of (poly)phenols and anti-diabetic medication in type 2 diabetes management: a meta-analysis of randomized controlled human trials.

PURPOSE: (Poly)phenols have been reported to confer protective effects against type 2 diabetes but the precise association remains elusive. This meta-analysis aimed to assess the effects of (poly)phenol intake on well-established biomarkers in people with type 2 diabetes or at risk of developing diabetes. METHODS: A systematic search was conducted using the following selection criteria: (1) human randomized controlled trials involving individuals with prediabetes and type 2 diabetes; (2) one or more of the following biomarkers: glucose, glycated haemoglobin (HbA1c), insulin, pro-insulin, homeostatic model assessment of insulin resistance (HOMA-IR), islet amyloid polypeptide (IAPP)/amylin, pro-IAPP/pro-amylin, glucagon, C-peptide; (3) chronic intervention with pure or enriched mixtures of (poly)phenols. From 488 references, 88 were assessed for eligibility; data were extracted from 27 studies and 20 were used for meta-analysis. The groups included in the meta-analysis were: (poly)phenol mixtures, isoflavones, flavanols, anthocyanins and resveratrol. RESULTS: Estimated intervention/control mean differences evidenced that, overall, the consumption of (poly)phenols contributed to reduced fasting glucose levels (- 3.32 mg/dL; 95% CI - 5.86, - 0.77; P = 0.011). Hb1Ac was only slightly reduced (- 0.24%; 95% CI - 0.43, - 0.044; P = 0.016) whereas the levels of insulin and HOMA-IR were not altered. Subgroup comparative analyses indicated a stronger effect on blood glucose in individuals with diabetes (- 5.86 mg/dL, 95% CI - 11.34, - 0.39; P = 0.036) and this effect was even stronger in individuals taking anti-diabetic medication (- 10.17 mg/dL, 95% CI - 16.59, - 3.75; P = 0.002). CONCLUSIONS: Our results support that the consumption of (poly)phenols may contribute to lower glucose levels in individuals with type 2 diabetes or at risk of diabetes and that these compounds may also act in combination with anti-diabetic drugs.

The dose-response effect on polyphenol bioavailability after intake of white and red wine pomace products by Wistar rats.

Wine pomace by-products are an important source of phenolic acids with significant health benefits. However, phenolic acid bioavailability in vivo has been little studied and there are few comparative studies on bioavailability between red and white wine pomace and the effect of intake of different doses. The qualitative and quantitative profile of phenolic acid metabolites in plasma and urine samples from Wistar rats was obtained by gas chromatography/mass detection, after oral administration of four doses (50, 100, 150, and 300 mg) of both the red and the white wine pomace products (rWPP and wWPP, respectively). The antioxidant capacity of the plasma samples assessed by both the ABTS and the FRAP levels was also evaluated. The results showed that neither the bioavailability nor the antioxidant capacity in vivo of the rWPP increased at high doses. However, both parameters were dependent on the intake of the wWPP.