High Molecular Weight Polyphenols Research Articles

Mathematical modeling of bioactive extraction from cashew apple: Maxwell-Stefan approach to resolve effect of internal diffusivity and external mass transfer

Every year 2.2 giga-tons of cashew apples are produced and 80 % (unutilized fruit) of them are wasted and contain useful bioactives such as polyphenols and tannins (high molecular weight polyphenols). These bioactives can be separated using extraction: the nutraceutical value of which is of the order of 1 billion USD/year. However, extraction kinetics are normally fitted to simple phenomenological models. These models fail to establish the effect of shrinkage, temperature, thermodynamic parameters, and internal resistances on diffusion of solute. Hence, the objective of this study was to develop a Maxwell-Stefan model that can overcome the above shortcomings and optimize the extraction process of bioactives from cashew apples. The optimized parameters for the extraction process obtained were − solid:solvent ratio- 1:6, particle size (of solid) 125–250 μm, and the extraction temperature as 30 °C. The non-random two liquid (NRTL) activity coefficient model was first used to capture the thermodynamics of extraction effectively, followed by its utilization in the development of Maxwell-Stefan model to resolve the effect of internal diffusivity and external mass transfer coefficient. The model gave a good fit (R2 > 0.90) for all the parameters and could thus predict the extraction data greatly for all operating parameters including temperature, particle size, and solid:solvent ratio. This makes it eminently suitable for scale-up studies.

Valorization of long-neglected spruce bark and bark-press effluents through integrated utilization of stilbenoids and pectin

Wood bark has exclusively been used for energy at pulp mills, while long-neglected, this huge biomass resource has great potential for valorization. To maximize its value in new ways, here we propose using both fresh (industrial) spruce bark and its bark-press effluents as sustainable sources of natural stilbenoids and pectin. Ultrafiltration removed approximately 90% of the high molecular weight polyphenols as well as enriched stilbenoids from bark-press effluents. Based on a techno-economic analysis, the forest industry would obtain greater revenue potential up to €100 per ton of bark by processing bark side streams compared to their traditional combustion-based strategy if implementing the improved debarking technology. Overall the valorization of stilbenoids and pectin from bark-press effluents or spruce bark offers a promising strategy to produce bio-based, high-value UV-filter ingredients as alternatives to fossil-based ones, and high-grade pectin in an economic feasible and potentially environmentally friendly bolt-on process to the existing mills.

Effect of fermentation time and temperature on the of polyphenol compounds change of different Congou black tea

This study evaluated the effects of fermentation time and temperature on the content of high molecular weight polyphenol mitochondrial activation factors (MAFs) and other polyphenols in Congou black tea using high-performance liquid chromatography (HPLC). There were two broad chromatographic peaks in the HPLC spectra of MAFs: MAFs-1 (16.163 min) and MAFs-2 (34.31 min); MAFs-2 was satisfactorily analyzed by HPLC, with separation by paper chromatography. The MAFs-2 contents increased gradually in different varieties of Congou black tea as the fermentation time and temperature increased; the maximum MAFs-2 content was 5.11% in Xiaoxianghong 21-3 after 8 hr of fermentation. The total polyphenols and catechins contents decreased, whereas the theabrownins contents increased as the fermentation time and temperature increased; the theaflavins and thearubigins contents in different Congou black teas showed different variation tendencies. Therefore, studies regarding changes in polyphenols during fermentation will help improve the quality of Congou black tea and enhance its health benefits. Novelty impact statement A new method for the determination of MAFs-2 by high-performance liquid chromatography combined with paper chromatography was established. The content of MAFs-2 increased initially and then stabilized as fermentation was continued from 2 to 8 hr, it increased gradually as the fermentation temperature was increased from 23 to 37°C. These results provide a new analytical method for MAFs in black tea and a theoretical basis and technical guidance for improving the quality of Congou black tea.

Black tea decreases postprandial blood glucose levels in healthy humans and contains high-molecular-weight polyphenols that inhibit α-glucosidase and α-amylase in vitro: a randomized, double blind, placebo-controlled, crossover trial

Background: To prevent diabetes, it is important to control postprandial glycemic levels. Studies have suggested that consuming black tea decreases the risk of type 2 diabetes; however, only a few studies have examined the effects of black tea on postprandial glycemic control after consuming starch-rich foods. In addition, the mechanism underlying the suppression of postprandial glucose levels remains unclear.Objective: To investigate the effects of black tea on postprandial blood glucose levels in healthy humans and to identify the components of black tea that inhibit digestive enzymes.Methods: The inhibitory activity of black tea on digestive enzymes was measured, and the inhibitory components were fractionated. Healthy Japanese adults ingested 200 ml of black tea, and its effect on postprandial blood glucose and insulin levels were investigated. Results: Black tea dose-dependently inhibited α-glucosidase, sucrase, and α-amylase activity. The major components responsible for this inhibition were high–molecular-weight polyphenols. The galloyl moieties present in these compounds play an important role in their inhibitory activities. Two randomized, double-blind, placebo-controlled, crossover studies of healthy human subjects (total n = 46) were conducted to investigate the effect of black tea on blood glucose and insulin levels. Combined data from the two studies showed that black tea ingestion (200 mL) after cooked rice intake (200 g) significantly reduced the incremental area under the curve of glucose (P =.024) and insulin (P =.014) compared to placebo drink.Conclusions: The high–molecular-weight polyphenols in black tea inhibited α-glucosidase, sucrase, and α-amylase activity in a dose-dependent manner. Furthermore, black tea ingestion after eating cooked rice significantly reduced the incremental area under the curve of glucose and insulin. These effects of black tea could be attributed to the inhibition of digestive enzymes by high–molecular-weight polyphenols containing galloyl groups.Keywords: black tea, blood glucose, α-glucosidase, α-amylase, polyphenol

Comparative studies of urolithins and their phase II metabolites on macrophage and neutrophil functions

PurposeEllagitannins are high molecular weight polyphenols present in high quantities in various food products. They are metabolized by human and animal gut microbiota to postbiotic metabolites-urolithins, bioavailable molecules of a low molecular weight. Following absorption in the gut, urolithins rapidly undergo phase II metabolism. Thus, to fully evaluate the mechanisms of their biological activity, the in vitro studies should be conducted for their phase II conjugates, mainly glucuronides. The aim of the study was to comparatively determine the influence of urolithin A, iso-urolithin A, and urolithin B together with their respective glucuronides on processes associated with the inflammatory response.MethodsThe urolithins obtained by chemical synthesis or isolation from microbiota cultures were tested with their respective glucuronides isolated from human urine towards modulation of inflammatory response in THP-1-derived macrophages, RAW 264.7 macrophages, PBMCs-derived macrophages, and primary neutrophils.ResultsUrolithin A was confirmed to be the most active metabolite in terms of LPS-induced inflammatory response inhibition (TNF-α attenuation, IL-10 induction). The observed strong induction of ERK1/2 phosphorylation has been postulated as the mechanism of its action. None of the tested glucuronide conjugates was active in terms of pro-inflammatory TNF-α inhibition and anti-inflammatory IL-10 and TGF-β1 induction.ConclusionComparative studies of the most abundant urolithins and their phase II conjugates conducted on human and murine immune cells unambiguously confirmed urolithin A to be the most active metabolite in terms of inhibition of the inflammatory response. Phase II metabolism was shown to result in the loss of urolithins’ pharmacological properties.

Chemical composition and antibacterial activity of red murta (Ugni molinae Turcz.) seeds: an undervalued Chilean resource

Murta (Ugni molinae Turcz) is an endemic Chilean specie mostly used in medical, cosmetic, and food industries. However, during the industrial processing of murta fruits, the biomass containing the seeds is discarded as an industrial byproduct that does not find significant uses yet. This work is a first approach to valorize murta biomass through the identification and quantification of principal chemical constituents and exploring their antibacterial properties. The proximal analysis revealed that murta seeds exhibited significant content of raw fiber (64%), crude fat (14%), crude protein (12%), and low levels of ashes (1.5%) and minerals (0.04–0.23%). Dietary fiber was mainly composed of lignin, cellulose, pectin, and hemicellulose. Polyunsaturated fatty acids (89.0%), monounsaturated fatty acids (7.7%), and saturated fatty acids (3.3%) were the main constituents of seed oils. The arginine, asparagine, glutamic acid, and glycine were the primary protein constituent amino acids. Tannin fractions, total polyphenolic content, and oxygen radical absorbance capacity as antioxidant activity were measured. The chromatographic and mass spectrometric analysis (HPLC–MS/MS) confirmed the presence of several phenolic compounds like phenolic acids, flavonols, flavones, proanthocyanidins, and high molecular weight polyphenols. The murta seed extract showed high antibacterial activity against both Gram positive (Staphylococcus aureus, Bacillus cereus, and Streptococcus pyogenes) and Gram negative (Escherichia coli, Salmonella typhi, and Pseudomonas aeruginosa) bacterial strains. Murta seeds could be considered as a new source of nutritional components and bioactive compounds for different nutraceutical and food applications.

Study of anticorrosive coatings based on high and low molecular weight polyphenols extracted from the Pine radiata bark

In this work, two primers with organic corrosion inhibitors were extracted from Pinus radiata bark, from the waste generated by the timber and paper industries. The process resulted in a water-soluble fraction (WSF) and water-insoluble fraction (WIF). The additives were incorporated in a two-component (2 K) primer based on epoxy-polyamide resin with a ratio formulation of λ = 0.85 (PVC = 34.79). Spectroscopy techniques, such as electron paramagnetic resonance (EPR), high-performance liquid chromatography (HPLC), Raman spectroscopy, and electrochemical impedance spectroscopy (EIS) were used for both the extract and coating characterizations. Coating performances were obtained in the order of 109 Ω. cm2 for the impedance, and the systems were simulated using a circuit (R1(Q1(R2(Q2(R3(R4C))))). The formation of tannin-Fe complexes was demonstrated using RAMAN spectroscopy.

Long term effects of olive mill wastewaters application on soil properties and phenolic compounds migration under arid climate

The principal objective of the present study has been to investigate the long term application effects of olive mill wastewaters (OMWW) on the main properties of a Mediterranean soil under arid climate. In addition the migration dynamic and evolution of phenolic compounds in the different soil layers over time and according to the OMWW amount added have been studied.Results have showed that the irrigation of sandy soils by different doses of OMWW has influenced the soil physicochemical and microbiological characteristics. However, a slight change in the granulometric composition of soil treated with OMWW has been distinguished. The study of the phenolic compounds dynamic has showed the migration of these compounds further than 120 cm soil depth. The comparison of the different spectra obtained by the high pressure liquid chromatography (HPLC) technique has explained that the high molecular weight polyphenols which have been retained in the upper soil layers. However, the low molecular weight phenolic compounds have been detected in depth. All the results obtained have proved that the dose of 50 m3 ha−1 has been the most suitable for the soil studied.

Synthesis of maleilated polyflavonoids and lignin as functional bio-based building-blocks

Polyflavonoids and lignin from Pinus radiata (D. Don.) biomass were esterified with maleic anhydride by several synthesis pathways (22 °C, 24 h). Influence of the solvent (dimethylformamide (DMF), DMF/H2O, acetone, formamide)-, the catalyst-type (H2SO4, NaHCO3), and the NaHCO3-change (70 and 100 mmol) on the esterification yield, and the degree of substitution (DS) were estimated. The effect of the maleilation on structural features was assessed by spectroscopy (FT-IR, UV–vis, RMN), and molecular exclusion chromatography. FT-IR, and 1H-NMR provide valuable insight regarding the esterification extent. The results show that esterification of high molecular weight polyphenols exhibited reasonable yields (80–95 wt.%). A significant influence of the solvent-, and the catalyst was observed. Synthesis in formamide, as well as by the highest charge of the alkaline catalyst, exhibited the best performance toward the polyphenol´s modification. Maleilation efficiency was strongly influenced by the polyphenol-type. Non-water soluble polyflavonoid derivatives exhibited the highest DS/monomer unit regardless the synthesis conditions. Carboxylated polyphenols from radiata pine may be used as functional co-polymer for new kinds of material applications.

The Oxidative Activity of Ellagitannins Dictates Their Tendency To Form Highly Stabilized Complexes with Bovine Serum Albumin at Increased pH

Many food and forage plants contain tannins, high molecular weight polyphenols that characteristically interact strongly with protein, forming complexes that affect taste, nutritional quality, and the health of the consumer. In the present study, the interaction between bovine serum albumin (BSA) and each of seven hydrolyzable tannins or epigallocatechin gallate was examined. The objective was to define the effect of tannin oxidation, measured as oxidative activity (browning) or as oxidizability (degradation monitored by HPLC), on the formation on highly stabilized tannin-protein complexes and to determine how the reaction depended on the pH conditions. Gel electrophoresis and MALDI-TOF-MS were used to assess the formation of tannin-protein complexes. The results showed that tannin oxidizability was directly correlated with the tendency of the tannins to form highly stabilized complexes with BSA at increased pH (7.6). However, at slightly lower pH (6.7), other tannin features, such as the size and flexibility of the tannin, appeared to dictate the formation of highly stabilized tannin-protein complexes.

Polyphenol-Aluminum Complex Formation: Implications for Aluminum Tolerance in Plants.

Natural polyphenols may play an important role in aluminum detoxification in some plants. We examined the interaction between Al(3+) and the purified high molecular weight polyphenols pentagalloyl glucose (940 Da) and oenothein B (1568 Da), and the related compound methyl gallate (184 Da) at pH 4 and 6. We used spectrophotometric titration and chemometric modeling to determine stability constants and stoichiometries for the aluminum-phenol (AlL) complexes. The structures and spectral features of aluminum-methyl gallate complexes were evaluated with quantum chemical calculations. The high molecular weight polyphenols formed Al3L2 complexes with conditional stability constants (β) ∼ 1 × 10(23) at pH 6 and AlL complexes with β ∼ 1 × 10(5) at pH 4. Methyl gallate formed AlL complexes with β = 1 × 10(6) at pH 6 but did not complex aluminum at pH 4. At intermediate metal-to-polyphenol ratios, high molecular weight polyphenols formed insoluble Al complexes but methyl gallate complexes were soluble. The high molecular weight polyphenols have high affinities and solubility features that are favorable for a role in aluminum detoxification in the environment.

Apples and cardiovascular health--is the gut microbiota a core consideration?

There is now considerable scientific evidence that a diet rich in fruits and vegetables can improve human health and protect against chronic diseases. However, it is not clear whether different fruits and vegetables have distinct beneficial effects. Apples are among the most frequently consumed fruits and a rich source of polyphenols and fiber. A major proportion of the bioactive components in apples, including the high molecular weight polyphenols, escape absorption in the upper gastrointestinal tract and reach the large intestine relatively intact. There, they can be converted by the colonic microbiota to bioavailable and biologically active compounds with systemic effects, in addition to modulating microbial composition. Epidemiological studies have identified associations between frequent apple consumption and reduced risk of chronic diseases such as cardiovascular disease. Human and animal intervention studies demonstrate beneficial effects on lipid metabolism, vascular function and inflammation but only a few studies have attempted to link these mechanistically with the gut microbiota. This review will focus on the reciprocal interaction between apple components and the gut microbiota, the potential link to cardiovascular health and the possible mechanisms of action.

Antioxidant activity of various lignins and lignin-related phenylpropanoid units with high and low molecular weight

Abstract The antioxidant activities (AoAs) of 50 different technical lignins have been determined. The lignins of various botanical origins (annual plants, coniferous trees, and deciduous trees) were isolated and fractionated by different techniques (delignification by alkali, kraft process, fast pyrolysis, and hydrolysis). The structure and the functionality of lignins were characterized by functional group analyses (phenolic OH, carboxyl, and methoxyl groups), analytical pyrolysis pyrolysis/gas chromatography/mass spectrometry/flame ionization detector (Py-GC/MS/FID), electron paramagnetic resonance, size exclusion chromatography, and titrimetric methods, and the AoAs were evaluated as the capacity to scavenge the DPPH· and ABTS·+ free radicals. The relationship between the lignin structure and the AoA was characterized by pair correlation, partial correlation, and multivariate regression analyses, including correlated components regression. The results were compared with those of lignin model compounds and low molecular weight phenylpropanoids. It has been shown that molecular weight does not influence essentially the AoA of lignins. There is a relationship between the activities of low and high molecular weight polyphenols; their mechanisms of action are also similar. The structure-related AoA of lignins has been quantified for the first time.

Mechanisms of cholesterol and saturated fatty acid lowering by Quillaja saponaria extract, studied by in vitro digestion model.

Quillaja saponin extracts are known to reduce plasma cholesterol levels in humans. Here we study the mechanism of this effect with Quillaja Dry saponin extract (QD). In vitro model of triglyceride lipolysis is used to quantify the effect of QD on the solubilization of cholesterol and of the lipolysis products (fatty acids and monoglycerides) in the dietary mixed micelles (DMM). We found that QD extract decreases significantly both the cholesterol (from 80% to 20%) and saturated fatty acids (SFA, from 70% to 10%) solubilised in DMM. Series of dedicated experiments prove that QD may act by two mechanisms: (1) direct precipitation of cholesterol and (2) displacement of cholesterol from the DMM. Both mechanisms lead to increased cholesterol precipitation and, thus, render cholesterol bio-inaccessible. We prove also that the saponin molecules are not the active component of QD, because highly purified Quillaja extract with very similar saponin composition does not exhibit cholesterol-lowering or SFA-lowering effect. The effect of QD extract on cholesterol solubilisation is most probably caused by the high-molecular weight polyphenol molecules, present in this extract. The reduced SFA solubilisation is caused by Ca(2+) ions of relatively high concentration (1.25 wt%), also present in QD extract, which precipitate the fatty acids into calcium soaps.

Assessment of Antioxidant Capacity, Anti-collagenase and Anti-elastase Assays of Malaysian Unfermented Cocoa Bean for Cosmetic Application

Recent trends in anti-aging research projected the use of antioxidant compound derived from botanical products. Phenolic acids, flavonoids and high molecular weight polyphenols are some of antioxidants which are able to protect human skin against the harmful effects of ultraviolet irradiation, i.e. photoaging and skin cancer development. Various studies have demonstrated cocoa beans to contain polyphenols and possess health promoting effects mainly on antiradical property. In this study, the HPLC/DAD quantification of (–)-epicatechin from PBC123 and PBC140 Malaysian unfermented cocoa bean extracts (CBEs) were 121.01 and 118.09 mg/g DW, whereas concentration of (+)-catechin were 6.65 and 6.53 mg/g DW, respectively with no significant differences (p>0.05). In term of antioxidant capacity, Ferric reducing/antioxidant power of the respective clones were assayed at 822.10 and 795.99 mM FeSO4/g DW. Inhibition of proteinases expression induces by reactive oxygen species were exhibited in the anti-collagenase and anti-elastase assays. The anti-collagenase activity of PBC123 and PBC140 were 62.99% and 59.96% whereas anti-elastase has been measured at 36.60% and 15.75%, respectively. Positive and high correlation were observed within epicatechin content (1), FRAP (2) and anti-collagenase (3) with significant relationships for both PBC123 and PBC140 (r12=0.901, r13=0.768 and r23=0.908). A statistical One-Way ANOVA showed that there was no significant difference obtained between PBC123 and PBC140 in terms of epicatechin, FRAP and anti-collagenase assays, however, significant difference was observed from anti-elastase assessment (p<0.05).These results indicate unfermented PBC123 clone as a potential source of natural ingredient in a cosmetic industry.

Antagonist Effects of Veratric Acid against UVB-Induced Cell Damages

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human epidermis, resulting in inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effect of UV irradiation is essential. In recent years naturally occurring herbal compounds such as phenolic acids, flavonoids, and high molecular weight polyphenols have gained considerable attention as beneficial protective agents. The simple phenolic veratric acid (VA, 3,4-dimethoxybenzoic acid) is one of the major benzoic acid derivatives from vegetables and fruits and it also occurs naturally in medicinal mushrooms which have been reported to have anti-inflammatory and anti-oxidant activities. However, it has rarely been applied in skin care. This study, therefore, aimed to explore the possible roles of veratric acid in protection against UVB-induced damage in HaCaT cells. Results showed that veratric acid can attenuate cyclobutane pyrimidine dimers (CPDs) formation, glutathione (GSH) depletion and apoptosis induced by UVB. Furthermore, veratric acid had inhibitory effects on the UVB-induced release of the inflammatory mediators such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of veratric acid on human skin. Overall, results demonstrated significant benefits of veratric acid on the protection of keratinocyte against UVB-induced injuries and suggested its potential use in skin photoprotection.

Soil microbial communities respond differently to three chemically defined polyphenols

High molecular weight polyphenols (e.g. tannins) that enter the soil may affect microbial populations, by serving as substrates for microbial respiration or by selecting for certain microbes. In this study we examined how three phenolic compounds that represent some environmentally widespread tannins or their constituent functional groups were respired by soil microorganisms and how the compounds affected the abundance and diversity of soil bacteria and archaea, including ammonia oxidizers. An acidic, silt loam soil from a pine forest was incubated for two weeks with the monomeric phenol methyl gallate, the small polyphenol epigallocatechin gallate, or the large polyphenol oenothein B. Respiration of the polyphenols during the incubation was measured using the Microresp™ system. After incubation, metabolic diversity was determined by community level physiological profiling (CLPP), and genetic diversity was determined using denaturing gradient gel electrophoresis (DGGE) analysis on DNA extracted from the soil samples. Total microbial populations and ammonia-oxidizing populations were measured using real time quantitative polymerase chain reaction (qPCR). Methyl gallate was respired more efficiently than the higher molecular weight tannins but not as efficiently as glucose. Methyl gallate and epigallocatechin gallate selected for genetically or physiologically unique populations compared to glucose. None of the polyphenols supported microbial growth, and none of the polyphenols affected ammonia-oxidizing bacterial populations or ammonia-oxidizing archaea. Additional studies using both a wider range of polyphenols and a wider range of soils and environments are needed to elucidate the role of polyphenols in determining soil microbiological diversity.

Recent Applications of Mass Spectrometry in the Study of Grape and Wine Polyphenols

Polyphenols are the principal compounds associated with health benefic effects of wine consumption and in general are characterized by antioxidant activities. Mass spectrometry is shown to play a very important role in the research of polyphenols in grape and wine and for the quality control of products. The soft ionization of LC/MS makes these techniques suitable to study the structures of polyphenols and anthocyanins in grape extracts and to characterize polyphenolic derivatives formed in wines and correlated to the sensorial characteristics of the product. The coupling of the several MS techniques presented here is shown to be highly effective in structural characterization of the large number of low and high molecular weight polyphenols in grape and wine and also can be highly effective in the study of grape metabolomics.

Anti-candida potential of red fruits: Antifungal and anti-biofilm effects

In the context of the prevention of dental caries, the cranberry fruit (Vaccinium macrocarpon), thanks to its richness in high molecular weight polyphenols, previously demonstrated anti-cariogenic properties, inhibiting biofilm formation of cariogenic bacteria. The antifungal activity of a dry extract of this fruit and three other red fruits (Rubus idaeus, Vaccinium myrtillus and Malpighia punicifolia) was assessed on Candida albicans and C. glabrata yeasts, which are oral cavity commensals, with a planktonic mode of growth. Moreover, the activity of these fruit extracts was studied against Candida spp. biofilms. A first approach was to evaluate the ability of yeasts to adhere to untreated polystyrene surfaces and to form biofilms in YNB medium supplemented with fruit extracts (0.02–40mg/mL). A second approach was to pretreat the polystyrene surfaces by fruit extracts (2–40mg/mL) and then to evaluate the ability of yeasts to both adhere to these surfaces and form biofilms. The MIC determination of the four extracts showed a lack of antifungal activity. Regarding the anti-adhesion and anti-biofilm effects, in the case of the first approach, a significant anti-adhesion activity was obtained with cranberry extract, using concentrations ≥1.25mg/mL (C. albicans) and ≥2.5mg/mL (C. glabrata). Its activity was studied on five other strains of C. albicans and C. glabrata in the second approach. In conclusion, this preliminary work demonstrated the anti-adhesion potency of cranberry extract on Candida spp, but this activity was strain-dependent.

Urolithins Are the Main Urinary Microbial-Derived Phenolic Metabolites Discriminating a Moderate Consumption of Nuts in Free-Living Subjects with Diagnosed Metabolic Syndrome

Walnuts ( Juglans regia L.), hazelnuts ( Corylus avellana L.), and almonds ( Prunus dulcis Mill.) are rich sources of ellagitannins and proanthocyanidins. Gut microbiota plays a crucial role in modulating the bioavailability of these high molecular weight polyphenols. However, to date there are no studies evaluating the capacity to produce nut phenolic metabolites in subjects with metabolic syndrome (MetS), a pathology associated with an altered gut bacterial diversity. This study applied a LC-MS targeted approach to analyze the urinary excretion of nut phenolic metabolites in MetS subjects following 12 weeks of nut consumption, compared to sex- and age-matched individuals given a nut-free control diet. Metabolites were targeted in both hydrolyzed and nonhydrolyzed urine by LC-PDA-QqQ-MS/MS analysis, and identification of metabolites lacking available standards was confirmed by LC-ESI-ITD-FT-MS. Ellagitannin-derived urolithins A and B significantly increased after the nut-enriched-diet, urolithins C and D were also detected, and a complex combination of urolithin-conjugated forms was observed in nonhydrolyzed urine, confirming an extensive phase II metabolism after absorption. In contrast, no significant increases in proanthocyanidin microbial metabolites were observed in urine following nut consumption. Because the intestinal microbiota of the subjects in this study could catabolize ellagitannins into a wide range of urolithins, further research is strongly warranted on the in vivo potential of these microbial metabolites in reducing cardiometabolic risk.