Post-anthesis thermal stress induces differential accumulation of bioactive compounds in field-grown barley.

BACKGROUND: Barley (Hordeum vulgare L.) is a healthy grain because of its high content of dietary fibre and phenolic compounds. It faces periods of high temperature during grain filling, frequently reducing grain weight. Heat stress may also affect some of the bioactive compounds present in the grain. To produce quality grains that provide nutritional and health benefits, it is important to understand the effect of environmental stresses on the quantity and quality of bioactive compounds. RESULTS: We have studied the effect of post-anthesis thermal stress on barley bioactive compounds and antioxidant capacity under Mediterranean field conditions during two consecutive growing seasons in four barley genotypes. Thermal stress affected grain weight and size and changed the relative composition of bioactive compounds. The relationship between heat stress and grain ß-glucans and arabinoxylans content was indirect, as the resulting increases in concentrations were due to the lower grain weight under stress. Conversely, heat stress had a significant direct impact on some phenolic compounds, increasing their concentrations differentially across genotypes, which contributed to an improvement in antioxidant capacity of up to 30%. CONCLUSION: Post-anthesis thermal stress had a significant effect on ß-glucans, arabinoxylans, phenolic compound concentration and antioxidant capacity of barley grains. Final grain quality could, at least partially, be controlled in order to increase the bioactive concentrations in the barley grain, by cultivation in growing areas prone to heat stress. Late sowings or late flowering genotypes could also be considered, should a premium be implemented to compensate for lower yields. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Metabolic and Microbial Modulation of the Large Intestine Ecosystem by Non-Absorbed Diet Phenolic Compounds: A Review.

Phenolic compounds represent a diverse group of phytochemicals whose intake is associated with a wide spectrum of health benefits. As consequence of their low bioavailability, most of them reach the large intestine where, mediated by the action of local microbiota, a series of related microbial metabolites are accumulated. In the present review, gut microbial transformations of non-absorbed phenolic compounds are summarized. Several studies have reached a general consensus that unbalanced diets are associated with undesirable changes in gut metabolism that could be detrimental to intestinal health. In terms of explaining the possible effects of non-absorbed phenolic compounds, we have also gathered information regarded their influence on the local metabolism. For this purpose, a number of issues are discussed. Firstly, we consider the possible implications of phenolic compounds in the metabolism of colonic products, such as short chain fatty acids (SCFA), sterols (cholesterol and bile acids), and microbial products of non-absorbed proteins. Due to their being recognized as affective antioxidant and anti-inflammatory agents, the ability of phenolic compounds to counteract or suppress pro-oxidant and/or pro-inflammatory responses, triggered by bowel diseases, is also presented. The modulation of gut microbiota through dietetic maneuvers including phenolic compounds is also commented on. Although the available data seems to assume positive effects in terms of gut health protection, it is still insufficient for solid conclusions to be extracted, basically due to the lack of human trials to confirm the results obtained by the in vitro and animal studies. We consider that more emphasis should be focused on the study of phenolic compounds, particularly in their microbial metabolites, and their power to influence different aspects of gut health.

Gallic acid is an active component for the anticarcinogenic action of grape seed procyanidins in pancreatic cancer cells.

The aim of the present work was to evaluate the effects of a grape seed procyanidin extract (GSPE) on proliferation and apoptosis in the pancreatic adenocarcinoma cell line MIA PaCa-2 and identify the components of the extract with higher activity. The effects of the extract were analyzed on the proliferation and apoptosis processes in MIA PaCa-2 cells, as well as in the levels of the apoptosis markers Bcl-2 and Bax, the mitochondrial membrane potential, and reactive oxygen species levels. Finally, the components of the extract with higher effects were elucidated using enriched fractions of the extract and pure compounds. The results showed that GSPE inhibits cell proliferation and increases apoptosis in MIA PaCa-2 cells, which is primarily mediated by the downregulation of the antiapoptotic protein Bcl-2 and the depolarization of the mitochondrial membrane. GSPE also reduced the formation of reactive oxygen species. The component of the extract that possesses the highest antiproliferative and proapoptotic activity was gallic acid. In conclusion, GSPE acts as anticarcinogenic in MIA PaCa-2 cells, with gallic acid as the major single active constituent of the extract.

Unlocking Phenolic Potential: Determining the Optimal Grain Development Stage in Hull-Less Barley Genotypes with Varying Grain Color.

Barley is rich in phenolic compounds, providing health benefits and making it a valuable addition to a balanced diet. However, most studies focus on these compounds at barley's final maturity, neglecting their synthesis during grain development and its impact on barley quality for food applications. This study investigates phenolic profiles during grain development in four hull-less barley genotypes with different grain colors, specifically bred for food applications. The objectives were to determine the phenolic profile and identify the optimal maturity stage for maximum phenolic content and antioxidant capacity. Using UPLC-MS/MS and in vitro antioxidant capacity assays, results show that total phenolic compounds decrease as grain matures due to increased synthesis of reserve components. Flavan-3-ols, phenolic acids, and flavone glycosides peaked at immature stages, while anthocyanins peaked at physiological maturity. The harvest stage had the lowest phenolic content, with a gradient from black to yellow, purple, and blue genotypes. Antioxidant capacity fluctuated during maturation, correlating positively with phenolic compounds, specially bound phenolic acids and anthocyanins. These findings suggest that early harvesting of immature grain can help retain bioactive compounds, promoting the use of immature barley grains in foods. To support this market, incentives should offset costs associated with decreased grain weight.

Effect of Barley and Oat Consumption on Immune System, Inflammation and Gut Microbiota: A Systematic Review of Randomized Controlled Trials.

PURPOSE OF REVIEW: The aim of this systematic review was to investigate the effects of whole grain Avena sativa and Hordeum vulgare L., or their isolated fractions, on immune and inflammatory functions, as well as their influence on gut microbiota. A structured literature search was undertaken in line with PRISMA guidelines. Randomized controlled trials (RCTs) that investigated the effects of oats or barley consumption in adults and reported ≥ 1 of the following: C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), IL-2, IL-8, IL-18, lipopolysacharide binding protein (LBP) or gut microbiota-related outcomes, were included. RECENT FINDINGS: A total of 16 RCTs were included, among which 6 studies recruited metabolically at-risk population, including individuals with overweight and obesity, metabolic syndrome or hypercholesterolemia. Additionally, 3 trials involved young healthy population, 5 trials targeted older individuals (aged over 50 years), and 2 studies encompassed populations with other disease states. A total of 1091 individuals were included in the evaluation of short-term (up to 14 days) and long-term (beyond 14 days, up to 90 days) supplementation with oats or barley-based products. 9 studies measured inflammatory biomarkers and 5 of them reported significant reductions, specifically in long-term studies. Notably, no evidence of anti-inflammatory benefits was found in healthy individuals, whereas studies involving metabolically at-risk populations showed promising reductions in inflammation. 13 studies measured the impact on gut microbiota, and collectively suggest that oats and barley food products can influence the composition of gut microbiota, associated in some cases with metabolic improvements. Oats and barley consumption may confer anti-inflammatory effects in metabolically at-risk populations and influence gut microbiota outcomes. However, no anti-inflammatory benefits were observed in healthy individuals. Results from this systematic review suggests caution in interpreting findings due to limited trials and variations in interventions and health conditions.

Metabolic profiling of (poly)phenolic compounds in mouse urine following consumption of hull-less and purple-grain barley.

The present study attempted for the first time to investigate the metabolic fate of (poly)phenolic compounds provided by a hull-less and purple grain barley genotype biofortified in anthocyanins. Balb/c mice were supplemented either with standard purified diet (SD) or whole-grain barley supplemented diet (WGB) for six weeks. Subsequently, (poly)phenolic metabolites were determined in urine samples by UPLC-MS/MS, and the principal metabolic pathways were elucidated. Thirty-nine (poly)phenolics compounds were identified in WGB which were distributed between the free (58%) and bound (42%) fractions, encompassing anthocyanins, phenolic acids, flavan-3-ols and flavones. Upon WGB intake, forty-two (poly)phenolic metabolites were identified, predominantly comprising phase-II sulphate, glucuronide, and/or methylated conjugates, along with colonic catabolites. Noteworthy metabolites included peonidin-3-O-glucuronide, peonidin-3-O-6''-O-malonylglucoside, and peonidin-3-O-glucoside among anthocyanins; hydroxyphenylpropanoic acid-O-sulphate among phenolic acids; and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone-O-sulphate among flavan-3-ols. Metabolites like phenylpropionic, phenylacetic, hydroxybenzoic, and hippuric acids were found in both WGB and SD groups, with higher levels after barley consumption, indicating both endogenous and polyphenolic metabolism origins. Overall, this study offers valuable insights into the metabolism of (poly)phenols in purple barley, setting the stage for future investigations into the health benefits linked to the consumption of purple grain barley.

Hydroxytyrosol Induces Dyslipidemia in an ApoB100 Humanized Mouse Model.

SCOPE: Extra virgin olive oil has numerous cardiopreventive effects, largely due to its high content of (poly)phenols such as hydroxytyrosol (HT). However, some animal studies suggest that its excessive consumption may alter systemic lipoprotein metabolism. Because human lipoprotein metabolism differs from that of rodents, this study examines the effects of HT in a humanized mouse model that approximates human lipoprotein metabolism. METHODS AND RESULTS: Mice are treated as follows: control diet or diet enriched with HT. Serum lipids and lipoproteins are determined after 4 and 8 weeks. We also analyzed the regulation of various genes and miRNA by HT, using microarrays and bioinformatic analysis. An increase in body weight is found after supplementation with HT, although food intake was similar in both groups. In addition, HT induced the accumulation of triacylglycerols but not cholesterol in different tissues. Systemic dyslipidemia after HT supplementation and impaired glucose metabolism are observed. Finally, HT modulates the expression of genes related to lipid metabolism, such as Pltp or Lpl. CONCLUSION: HT supplementation induces systemic dyslipidemia and impaired glucose metabolism in humanized mice. Although the numerous health-promoting effects of HT far outweigh these potential adverse effects, further carefully conducted studies are needed.

A red-fleshed apple rich in anthocyanins improves endothelial function, reduces inflammation, and modulates the immune system in hypercholesterolemic subjects: the AppleCOR study.

The study determines the sustained and acute effects of a red-fleshed apple (RFA), rich in anthocyanins (ACNs), a white-fleshed apple (WFA) without ACNs, and an infusion from Aronia melanocarpa (AI) with an equivalent content of ACNs as RFA, on different cardiometabolic risk biomarkers in hypercholesterolemic subjects. A randomized, parallel study was performed for 6 weeks and two dose-response studies were performed at the baseline and after intervention. At 6 weeks, RFA consumption improved ischemic reactive hyperemia and decreased C-reactive protein and interleukine-6 compared to WFA consumption. Moreover, at 6 weeks, AI decreased P-selectin compared to WFA and improved the lipid profile. Three products reduced C1q, C4 and Factor B, and RFA and AI reduced C3. Although both RFA and AI have a similar ACN content, RFA, by a matrix effect, induced more improvements in inflammation, whereas AI improved the lipid profile. Anti-inflammatory protein modulation by proteomic reduction of the complement system and immunoglobulins were verified after WFA, AI and RFA consumption.

Flavanol metabolites distribute in visceral adipose depots after a long-term intake of grape seed proanthocyanidin extract in rats.

A considerable number of epidemiological investigations and intervention studies have supported an association between the intake of flavanol- and proanthocyanidin-containing foods and a decreased risk of metabolic diseases. Nonetheless, less is know about the capacity of tissues to accumulate flavanols and/or their metabolites. The main objective of the present study was to determine (n 20) plasma bioavailability and disposition in the liver, muscle, brown adipose tissue (BAT) and white adipose tissues (mesenteric and perirenal) in rats after a long-term consumption of three doses of grape seed phenolic extract (5, 25 and 50 mg/kg body weight) for 21 d in order to determine whether there is a dose-response relationship. Glucuronidated conjugates (total glucuronidated conjugates: C(5 mg/kg) 1·9; C(25 mg/kg) 6·4; C(50 mg/kg) 27·7 µmol/l plasma) followed by methyl glucuronidated conjugates (total methyl glucuronidated conjugates: C(5 mg/kg) 1·98; C(25 mg/kg) 4·48; C(50 mg/kg) 12·5 µmol/l plasma) were the main flavanol metabolites quantified in plasma, also detecting a dimer in its free form (C(25 mg/kg) 0·74; C(50 mg/kg) 0·79 µmol/l plasma). Each of the studied organs has a particular behaviour of accumulation and response to the assayed grape seed extract doses, with an exponential bioavailability-dose relationship in BAT, in which flavanols could play an important role in the reduction or prevention of obesity, modulating the functionality of that tissue.

Application of dried spot cards as a rapid sample treatment method for determining hydroxytyrosol metabolites in human urine samples. Comparison with microelution solid-phase extraction.

Two different rapid sample pretreatment strategies, dried spot cards, and microelution solid-phase extraction plates (µSPE), with ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) have been developed and validated for the determination of hydroxytyrosol and its metabolites in spiked human urine samples. Hydroxytyrosol, hydroxytyrosol-3'-O-glucuronide, hydroxytyrosol-4'-O-glucuronide, hydroxytyrosol-3-O-sulphate, and homovanillic alcohol-4'-O-glucuronide were used as the target compounds. Using the FTA DMPK-A dried urine spot card under optimum conditions, with 5 µL of preconcentrated urine volume and 100 µL of methanol/water (50/50, v/v) as the elution solvent, the extraction recovery (%R) of the compounds studied was higher than 80%, and the matrix effect (%ME) was less than 8%. The stability of these cards and punching at the centre or side of the card were also studied, obtaining an excellent stability after 7 days of storage and complete homogeneity across the surface of the dried drop. The different µSPE parameters that affect the efficiency were also studied, and under optimum conditions, the %R and the %ME were higher than 70% and lower than 17%, respectively. The linearity range in dried urine spot cards was 2.5-20 µM for all the metabolites, with the exception of hydroxytyrosol-3-O-sulphate and hydroxytyrosol, which were 0.3-70 µM and 2.5-50 µM respectively. With regards to µSPE, the linearity range was 0.5-5 µM for all the studied compounds, except for hydroxytyrosol-3-O-sulphate, which was 0.08-5 µM. The quantification limits (LOQs) were 0.3-2.5 µM and 0.08-0.5 µM in dried spot cards and in µSPE, respectively. The two developed methods were then applied and compared for determining hydroxytyrosol and its metabolites in human 24 h-urine samples after a sustained consumption (21 days) of a phenol-enriched virgin olive oil. The metabolites identified were hydroxytyrosol in its glucuronide and sulphate forms, homovanillic alcohol in its glucuronide and sulphate forms, homovanillic acid sulphate and hydroxytyrosol acetate sulphate.

Distribution of procyanidins and their metabolites in rat plasma and tissues in relation to ingestion of procyanidin-enriched or procyanidin-rich cocoa creams.

BACKGROUND: Procyanidins are extensively metabolized via phase-II and microbial enzymes. However, their distribution in the body is not well characterized. AIM: This study investigates the distribution of procyanidins (monomers and dimers) and their phase-II metabolites in plasma and tissues (thymus, heart, liver, testicle, lung, kidney, spleen and brain). METHODS: Wistar rats were fed with 1 g of cocoa cream (CC), 50 mg of procyanidin hazelnut skin extract (PE) and 50 mg PE in 1 g CC (PECC). The rats were killed at 0, 1, 1.5, 2, 3, 4 and 18 h after gavage, and the plasma and tissues were analyzed by UPLC-MS/MS. RESULTS: Epicatechin-glucuronide was the main metabolite in the plasma after the CC intake, with C(max) at 423 nM and t(max) at 2 h, and methyl catechin-glucuronide (301 nM, 2 h) was the main metabolite in the plasma after the PE intake. As a result of the PECC enrichment, epicatechin-glucuronide (452 nM, 1.5 h) and catechin-glucuronide (297 nM, 2 h) were the main metabolites in the plasma. Methyl catechin-glucuronide was found in the liver after PE (8 nmol/g tissue, 4 h) and PECC (8 nmol/g, 1.5 h). The kidney was found to contain a high concentration of phase-II metabolites of procyanidins and is therefore thought to be the main site of metabolism of the compounds. Methyl catechin-sulfate (6.4 nmol/g, 4 h) was only quantified in the brain and after PE intake. Catechin metabolites were not found in the spleen or heart. Phenolic acids were detected in all tissues. CONCLUSIONS: The formulation of a product enriched or fortified with procyanidins is a way to increase their bioavailability, with clear effects on the plasmatic pharmacokinetics, and a greater accumulation of phenolic metabolites in such tissues as the liver, kidney, lung and brain.

Assessment of human inter-individual variability of phloretin metabolites in urine after apple consumption. AppleCOR study.

Purpose: This study aimed to assess the inter-individual variation in phloretin absorption and metabolism and to seek possible phloretin metabotypes following apple snack consumption. Methods: The excreted phloretin metabolites in 24 h urine samples were determined by UPLC-MS/MS in 62 volunteers after acute and sustained (6 weeks) interventions in a randomized and parallel study with a daily supplementation of 80 g of a low-phloretin (39.5 µmol) or a high-phloretin (103 µmol) freeze-dried apple snacks. Results: absorption estimated as phloridzin equivalents for 62 volunteers varied almost 70-fold ranging from 0.1% to 6.94% of phloretin glycoside intake. Volunteers were stratified into low, medium and high producers and by the balance between glucuronidation and sulphation. For 74% of the volunteers phloretin-O-glucuronide was the dominant urinary metabolite, especially at the higher phloretin glycoside intake and for higher producers. Sulphate conjugation assumed greater significance for the remaining volunteers especially for low producers. Females dominated glucuronide profile (64.1%) and males dominated the low excretion group. Analysis of plasma glucose and insulin at the start and end of the sustained study showed a trend towards modest reductions for high producers. Furthermore, plausible factors contributing to the inter-individual variation in phloretin uptake are discussed. Conclusions: extensive inter-individual variability exists in the excretion of phloretin phase-II conjugates following consumption of apple snacks, which could be related to oral microbiota phloridzin-hydrolysing activity, lactase non-persistence trait or the metabotype to which the subject belongs. There were inconsistent effects on post-prandial serum glucose concentrations but there was a tendency for decreases to be associated with higher excretion of phloretin phase-II conjugates. Trial registration: The acute and sustained studies were registered at ClinicalTrials.gov Identifier: NCT03795324.

Phenol metabolic fingerprint and selection of intake biomarkers after acute and sustained consumption of red-fleshed apple versus common apple in humans. The AppleCOR study.

The present study aimed to evaluate the metabolism and bioavailability of anthocyanins (ACN) and other phenolics from red-fleshed apple (RFA) and to define the intake biomarkers compared to common white-fleshed apple (WFA). Acute and sustained (6-week) interventions were combined in a randomized, controlled and parallel study with 121 hypercholesterolemic subjects. Another arm consuming ACN-rich infusion from aronia fruit (ARO) provided matched content and profile of ACN. Plasma, urine and faeces samples were analyzed using UPLC-MS/MS. Results showed higher bioavailability of ACN after ARO compared to RFA, showing a clear apple matrix effect. The dihydrochalcone phloretin-2'-O-glucuronide was the most discriminant intake biomarker of both apples. The urinary peonidin-3-O-galactoside was a good biomarker after both ARO and RFA intakes, whereas peonidin-O-arabinoside was reported to be specific from ARO. The elucidation of the phenolic metabolism and the selection of intake biomarkers is a promising approach to relate phenolic compounds and human health.

Bioavailability of phenols from a phenol-enriched olive oil.

Phenolic compounds are one of the main reasons behind the healthy properties of virgin olive oil (VOO). However, their daily intake from VOO is low compared with that obtained from other phenolic sources. Therefore, the intake of VOO enriched with its own phenolic compounds could be of interest to increase the daily dose of these beneficial compounds. To evaluate the effectiveness of enrichment on their bioavailability, the concentration of phenolic compounds and their metabolites in human plasma (0, 60, 120, 240 and 300 min) from thirteen healthy volunteers (seven men and six women, aged 25 and 69 years) was determined after the ingestion of a single dose (30 ml) of either enriched virgin olive oil (EVOO) (961·17 mg/kg oil) or control VOO (288·89 mg/kg oil) in a cross-over study. Compared with VOO, EVOO increased plasma concentration of the phenol metabolites, particularly hydroxytyrosol sulphate and vanillin sulphate (P < 0·05). After the consumption of VOO, the maximum concentration of these peaks was reached at 60 min, while EVOO shifted this maximum to 120 min. Despite these differences, the wide variability of results indicates that the absorption and metabolism of olive oil phenols are highly dependent on the individual.

Bioactive Compounds and Antioxidant Capacity in Pearling Fractions of Hulled, Partially Hull-Less and Hull-Less Food Barley Genotypes.

Three food barley genotypes differing in the presence or absence of husks were sequentially pearled and their fractions analyzed for ash, proteins, bioactive compounds and antioxidant capacity in order to identify potential functional food ingredients. Husks were high in ash, arabinoxylans, procyanidin B3, prodelphinidin B4 and p-coumaric, ferulic and diferulic bound acids, resulting in a high antioxidant capacity. The outermost layers provided a similar content of those bioactive compounds and antioxidant capacity that were high in husks, and also an elevated content of tocols, representing the most valuable source of bioactive compounds. Intermediate layers provided high protein content, ß-glucans, tocopherols and such phenolic compounds as catechins and bound hydroxybenzoic acid. The endosperm had very high ß-glucan content and relative high levels of catechins and hydroxybenzoic acid. Based on the spatial distribution of the bioactive compounds, the outermost 30% pearling fractions seem the best option to exploit the antioxidant capacity of barley to the full, whereas pearled grains supply ß-glucans enriched flours. Current regulations require elimination of inedible husks from human foods. However, due to their high content in bioactive compounds and antioxidant capacity, they should be considered as a valuable material, at least for animal feeds.

Variation in the Methylation of Caffeoylquinic Acids and Urinary Excretion of 3'-methoxycinnamic acid-4'-Sulfate After Apple Consumption by Volunteers.

INTRODUCTION: It has been reported that the phenolic metabolite 3'-methoxycinnamic acid-4'-sulfate generated from 5-O-caffeoylquinic acid may have potential benefits in human health. However, the variation in 3'- and 4'-methylation of 3',4'-dihydroxycinnamic acid and its impact on the yield of this sulfate metabolite is unclear and has been poorly studied. METHODS AND RESULTS: To address this aim, the excreted 3'-methoxy and 4'-methoxy metabolites in urine samples (24-h) are determined in 14 volunteers after an acute intake of 80 g of red-fleshed apple (RFA) or white-fleshed apple (WFA). These methoxy metabolites are also determined in the same volunteers in a second acute intake after a 6-week sustained consumption of the same products. CONCLUSION: Seven 3'-methoxy and seven 4'-methoxy metabolites are determined, i.e., the free cinnamic and corresponding phenylpropanoic acid, plus their sulfate, glucuronide, and glycine conjugates. In only six volunteers, five females and one male, is 4'-methylation preferred over 3'-methylation, but it is observed that an individual's 3'- : 4'-methylation ratio can change over time, and that the yield of 3'-methoxycinnamic acid-4'-sulfate is extremely variable, ranging from undetectable to 71% of the total C6 -C3 metabolites excreted, and any benefit accruing from this metabolite will not necessarily be available to all consumers.

Virgin Olive Oil Phenolic Compounds Modulate the HDL Lipidome in Hypercholesterolaemic Subjects: A Lipidomic Analysis of the VOHF Study.

SCOPE: The lipidomic analysis of high-density lipoprotein (HDL) could be useful to identify new biomarkers of HDL function. METHODS AND RESULTS: A randomized, controlled, double-blind, crossover trial (33 hypercholesterolaemic subjects) is performed with a control virgin olive oil (VOO), VOO enriched with its own phenolic compounds (FVOO), or VOO enriched with additional phenolic compounds from thyme (FVOOT) for 3 weeks. HDL lipidomic analyses are performed using the Lipidyzer platform. VOO and FVOO intake increase monounsaturated-fatty acids (FAs) and decrease saturated and polyunsaturated FAs in triacylglyceride (TAG) species, among others species. In contrast, FVOOT intake does not induce these FAs changes. The decrease in TAG52:3(FA16:0) after VOO intake and the decrease in TAG52:5(FA18:2) after FVOO intake are inversely associated with changes in HDL resistance to oxidation. After FVOO intake, the decrease in TAG54:6(FA18:2) in HDL is inversely associated with changes in HDL cholesterol efflux capacity. CONCLUSION: VOO and FVOO consumption has an impact on the HDL lipidome, in particular TAG species. Although TAGs are minor components of HDL mass, the observed changes in TAG modulated HDL functionality towards a cardioprotective mode. The assessment of the HDL lipidome is a valuable approach to identify and characterize new biomarkers of HDL function.

Metabolic Fate and Cardiometabolic Effects of Phenolic Compounds from Red-Fleshed Apple in Hypercholesterolemic Rats: A Comparative Study with Common White-Fleshed Apple. The AppleCOR Study.

The present study aims to investigate the metabolic fate and the cardiometabolic effects of phenolic compounds provided by a red-fleshed apple variety biofortified in anthocyanins (ACN). Wistar rats are fed with high-fat diet (HFD) to induce hypercholesterolemia and supplemented with red-fleshed apple (HFD+R), white-fleshed apple (HFD+W), or an ACN-rich infusion from aronia fruit (HFD+A) providing matched content and profile of ACN. Plasma biochemical parameters, histological analysis, and phenol biological metabolites are determined. Plasma, urine, and feces show a significant increase of ACN metabolites after HFD+R and HFD+A, while flavan-3-ols are significantly increased after HFD+W and dihydrochalcones derivatives increased after both apples supplementation. A cardioprotective effect is observed after both apples and aronia infusion supplementation in the reduction of aortic thickness. The kidney function is improved after all supplementations and a decrease in insulin plasma concentration after both apples supplementation (HFD+R and HFD+W) is also observed. The findings support that ACN without apple matrix can induce cardioprotective effects. ACN or flavan-3-ols, together with dihydrochalcones, compose a phenolic phytocomplex in red- and white-fleshed apples, respectively, which can act synergistically in the attenuation of cardiovascular outcomes in hypercholesterolemic rats.

Bioavailability of procyanidin dimers and trimers and matrix food effects in in vitro and in vivo models.

Among procyanidins (PC), monomers, such as catechin and epicatechin, have been widely studied, whereas dimer and trimer oligomers have received much less attention, despite their abundance in our diet. Recent studies have showed that as dimers and trimers could be important in determining the biological effects of procyanidin-rich food, understanding their bioavailability and metabolism is fundamental. The purpose of the present work is to study the stability of PC under digestion conditions, the metabolism and the bioavailability by using a combination of in vitro and in vivo models. Simultaneously, the matrix effect of a carbohydrate-rich food on the digestibility and bioavailability of PC is investigated. The results show a high level of stability of PC under gastric and duodenal digestion conditions. However, the pharmacokinetic study revealed limited absorption. Free forms of dimers and trimers have been detected in rat plasma, reaching the maximum concentration 1 h after oral intake of a grape seed extract.

Rapid analysis of procyanidins and anthocyanins in plasma by microelution SPE and ultra-HPLC.

In the analysis of biological samples, such as plasma or serum, the quantity of sample available is a critical parameter in most cases. A good approach is the use of the microelution SPE (µSPE) plates as sample pre-treatment technique in which the loaded sample volume is low. An off-line µSPE and ultra-performance LC-ESI-MS/MS (UPLC-ESI-MS/MS) method was developed and validated to determine procyanidins and anthocyanins in spiked plasma samples. The sample pre-treatment µSPE allowed the simultaneous determination of procyanidins and anthocyanins from plasma by using a small sample volume (350 µL) and without an evaporation step previous to the chromatographic analysis. Moreover, the use of UPLC technique allowed to determine the studied compounds at low concentration levels in a short analysis time (12.5 min approximately). Then, the developed method was applied to determine the studied compounds, procyanidins and anthocyanins, and their metabolites in rat plasma samples. Previously, the rats had consumed 5000 mg/kg of a grape pomace extract and the plasma was extracted 4 h after administration. The procyanidins catechin and epicatechin glucuronide, methyl catechin and epicatechin glucuronide, and methyl catechin and epicatechin sulphate were detected at µM concentration level, and the parent anthocyanins at nM.