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The American Journal of Clinical... Jun 2023Evidence suggests that the intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Evidence suggests that the intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive effects are linked to increases in cerebral and vascular blood flow or changes in the gut microbiota is currently unknown.
METHODS
A double-blind, parallel randomized controlled trial was conducted in 61 healthy older individuals aged 65-80 y. Participants received either 26 g of freeze-dried wild blueberry (WBB) powder (302 mg anthocyanins) or a matched placebo (0 mg anthocyanins). Endothelial function measured by flow-mediated dilation (FMD), cognitive function, arterial stiffness, blood pressure (BP), cerebral blood flow (CBF), gut microbiome, and blood parameters were measured at baseline and 12 wk following daily consumption. Plasma and urinary (poly)phenol metabolites were analyzed using microelution solid-phase extraction coupled with liquid chromatography-mass spectrometry.
RESULTS
A significant increase in FMD and reduction in 24 h ambulatory systolic BP were found in the WBB group compared with the placebo group (0.86%; 95% CI: 0.56, 1.17, P < 0.001; -3.59 mmHg; 95% CI: -6.95, -0.23, P = 0.037; respectively). Enhanced immediate recall on the auditory verbal learning task, alongside better accuracy on a task-switch task was also found following WBB treatment compared with placebo (P < 0.05). Total 24 h urinary (poly)phenol excretion increased significantly in the WBB group compared with placebo. No changes in the CBF or gut microbiota composition were found.
CONCLUSIONS
Daily intake of WBB powder, equivalent to 178 g fresh weight, improves vascular and cognitive function and decreases 24 h ambulatory systolic BP in healthy older individuals. This suggests that WBB (poly)phenols may reduce future CVD risk in an older population and may improve episodic memory processes and executive functioning in older adults at risk for cognitive decline. Clinical Trial Registration number in clinicaltrials.gov: NCT04084457.
Topics: Humans; Aged; Anthocyanins; Blueberry Plants; Phenols; Phenol; Powders; Fruit; Cognition; Memory, Short-Term; Double-Blind Method
PubMed: 36972800
DOI: 10.1016/j.ajcnut.2023.03.017 -
Journal of Medicinal Chemistry May 2022Phenols and phenolic ethers are significant scaffolds recurring both in nature and among approved small-molecule pharmaceuticals. This compendium presents the first... (Review)
Review
Phenols and phenolic ethers are significant scaffolds recurring both in nature and among approved small-molecule pharmaceuticals. This compendium presents the first comprehensive compilation and analysis of the structures of U.S. FDA-approved molecules containing phenol or phenolic ether fragments. This dataset comprises 371 structures, which are strongly represented by natural products. A total of 55 of the compounds described here are on the World Health Organization's list of essential medicines. Structural analysis reveals significant differences in the physicochemical properties imparted by phenols versus phenol ethers, each having benefits and drawbacks for drug developability. Despite trends over the past decade to increase the fraction of sp centers in drug leads, thereby "escaping flatland", phenols and phenolic ethers are represented in 62% of small-molecule drugs approved in 2020, suggesting that this aromatic moiety holds a special place in drugs and natural products.
Topics: Biological Products; Ethers; Pharmaceutical Preparations; Phenol; Phenols
PubMed: 35533692
DOI: 10.1021/acs.jmedchem.2c00223 -
Food Chemistry Jan 2022To explore the effects of phenolic binding on the structure and activity of lotus root polysaccharides (LRPs), five LRP-phenol complexes containing catechin...
To explore the effects of phenolic binding on the structure and activity of lotus root polysaccharides (LRPs), five LRP-phenol complexes containing catechin (61.22 mg/g), gallic acid (9.37 mg/g), ferulic acid (29.28 mg/g), chlorogenic acid (83.80 mg/g) or caffeic acid (14.80 mg/g) were prepared via noncovalent intermolecular interaction, respectively. The interaction was confirmed by the differences among LRPs, phenols and their complexes in ultraviolet-visible and Fourier-transform infrared spectra. The phenolic binding caused significant changes in the molecular weight (MW) distribution and aggregation behavior of LRPs, particularly their average MW (34.49 kDa) increased by 3.73-8.30 times. Compared to LRPs, the complexes all showed stronger antioxidant activities. Notably, the binding of catechin improved the macrophage-stimulating effect of LRPs, specifically promoting the NO production at normal condition and inhibiting the NO overproduction induced by lipopolysaccharide. The noncovalent interaction with phenolic compounds is a promising method for the structural and functional improvement of LRPs.
Topics: Antioxidants; Gallic Acid; Phenol; Phenols; Polysaccharides
PubMed: 34358960
DOI: 10.1016/j.foodchem.2021.130693 -
Mass Spectrometry Reviews 2023Extra virgin olive oil (EVOO) is largely used in Mediterranean diet, and it is also worldwide apprised not only for its organoleptic properties but also for its healthy... (Review)
Review
Extra virgin olive oil (EVOO) is largely used in Mediterranean diet, and it is also worldwide apprised not only for its organoleptic properties but also for its healthy effects mainly attributed to the presence of several naturally occurring phenolic and polyphenolic compounds (bio-phenols). These compounds are characterized by the presence of multiple phenolic groups in more or less complex structures. Their content is fundamental in defining the healthy qualities of EVOO and consequently the analytical methods for their characterization and quantification are of current interest. Traditionally their determination has been conducted using a colorimetric assay based on the reaction of Folin-Ciocalteu (FC) reagent with the functional hydroxy groups of phenolic compounds. Identification and quantification of the bio-phenols in olive oils requires certainly more performing analytical methods. Chromatographic separation is now commonly achieved by HPLC, coupled with spectrometric devices as UV, FID, and MS. This last approach constitutes an actual cutting-edge application for bio-phenol determination in complex matrices as olive oils, mostly on the light of the development of mass analyzers and the achievement of high resolution and accurate mass measurement in more affordable instrument configurations. After a short survey of some rugged techniques used for bio-phenols determination, in this review have been described the most recent mass spectrometry-based methods, adopted for the analysis of the bio-phenols in EVOOs. In particular, the sample handling and the results of HPLC coupled with low- and high-resolution MS and MS/MS analyzers, of ion mobility mass spectrometry and ambient mass spectrometry have been reported and discussed.
Topics: Phenols; Olive Oil; Tandem Mass Spectrometry; Phenol; Chromatography, High Pressure Liquid
PubMed: 34747510
DOI: 10.1002/mas.21744 -
Food & Function Mar 2024Dietary (poly)phenols have received great interest due to their potential role in the prevention and management of non-communicable diseases. In recent years, a high... (Review)
Review
Dietary (poly)phenols have received great interest due to their potential role in the prevention and management of non-communicable diseases. In recent years, a high inter-individual variability in the biological response to (poly)phenols has been demonstrated, which could be related to the high variability in (poly)phenol gut microbial metabolism existing within individuals. An interplay between (poly)phenols and the gut microbiota exists, with (poly)phenols being metabolised by the gut microbiota and their metabolites modulating gut microbiota diversity and composition. A number of (poly)phenol metabolising phenotypes or metabotypes have been proposed, however, potential metabotypes for most (poly)phenols have not been investigated, and the relationship between metabotypes and human health remains ambiguous. This review presents updated knowledge on the reciprocal interaction between (poly)phenols and the gut microbiome, associated gut metabotypes, and subsequent impact on human health.
Topics: Humans; Phenol; Phenols; Diet; Gastrointestinal Microbiome
PubMed: 38414364
DOI: 10.1039/d3fo04338j -
Molecules (Basel, Switzerland) Sep 2022Vitamin E, a collection of lipophilic phenolic compounds based on chroman-6-ol, has a rich and fascinating oxidative chemistry involving a range of intermediate forms,... (Review)
Review
Vitamin E, a collection of lipophilic phenolic compounds based on chroman-6-ol, has a rich and fascinating oxidative chemistry involving a range of intermediate forms, some of which are proposed to be important in its biological functions. In this review, the available electrochemical and spectroscopic data on these oxidized intermediates are summarized, along with a discussion on how their lifetimes and chemical stability are either typical of similar phenolic and chroman-6-ol derived compounds, or atypical and unique to the specific oxidized isomeric form of vitamin E. The overall electrochemical oxidation mechanism for vitamin E can be summarized as involving the loss of two-electrons and one-proton, although the electron transfer and chemical steps can be controlled to progress along different pathways to prolong the lifetimes of discreet intermediates by modifying the experimental conditions (applied electrochemical potential, aqueous or non-aqueous solvent, and pH). Depending on the environment, the electrochemical reactions can involve single electron transfer (SET), proton-coupled electron transfer (PCET), as well as homogeneous disproportionation and comproportionation steps. The intermediate species produced via chemical or electrochemical oxidation include phenolates, phenol cation radicals, phenoxyl neutral radicals, dications, diamagnetic cations (phenoxeniums) and -quinone methides. The cation radicals of all the tocopherols are atypically long-lived compared to the cation radicals of other phenols, due to their relatively weak acidity. The diamagnetic cation derived from α-tocopherol is exceptionally long-lived compared to the diamagnetic cations from the other β-, γ- and δ-isomers of vitamin E and compared with other phenoxenium cations derived from phenolic compounds. In contrast, the lifetime of the phenoxyl radical derived from α-tocopherol, which is considered to be critical in biological reactions, is typical for what is expected for a compound with its structural features. Over longer times via hydrolysis reactions, hydroxy -quinone hemiketals and quinones can be formed from the oxidized intermediates, which can themselves undergo reduction processes to form intermediate anion radicals and dianions. Methods for generating the oxidized intermediates by chemical, photochemical and electrochemical methods are discussed, along with a summary of how the final products vary depending on the method used for oxidation. Since the intermediates mainly only survive in solution, they are most often monitored using UV-vis spectroscopy, FTIR or Raman spectroscopies, and EPR spectroscopy, with the spectroscopic techniques sometimes combined with fast photoinitiated excitation and time-resolved spectroscopy for detection of short-lived species.
Topics: Benzoquinones; Chromans; Electron Spin Resonance Spectroscopy; Oxidation-Reduction; Phenol; Phenols; Protons; Solvents; Tocopherols; Vitamin E; alpha-Tocopherol
PubMed: 36234726
DOI: 10.3390/molecules27196194 -
Nutrients Aug 2022Plant-derived (poly)phenolic compounds have been undoubtedly shown to promote endocrine homeostasis through the improvement of diverse metabolic outcomes. Amongst... (Review)
Review
Plant-derived (poly)phenolic compounds have been undoubtedly shown to promote endocrine homeostasis through the improvement of diverse metabolic outcomes. Amongst diverse potential mechanisms, the prebiotic modulatory effects exerted by these compounds on the gut microbiota have supported their nutraceutical application in both experimental and clinical approaches. However, the comprehension of the microbiota modulatory patterns observed upon (poly)phenol-based dietary interventions is still in its infancy, which makes the standardization of the metabolic outcomes in response to a given (poly)phenol a herculean task. Thus, this narrative review sought to gather up-to-date information on the relationship among (poly)phenols intake, their modulatory effect on the gut microbiota diversity, and consequent metabolic outcomes as a supportive tool for the future design of experimental approaches and even clinical trials.
Topics: Gastrointestinal Microbiome; Microbiota; Phenol; Phenols; Prebiotics
PubMed: 36079768
DOI: 10.3390/nu14173510 -
Molecular Nutrition & Food Research Nov 2022This review focuses on the LC-MS characterization and quantification of dietary (poly)phenols and their metabolites. It draws attention to errors, omissions, and... (Review)
Review
This review focuses on the LC-MS characterization and quantification of dietary (poly)phenols and their metabolites. It draws attention to errors, omissions, and misunderstandings that appear frequently in published papers, and suggests strategies for their avoidance. Aspects covered include the use of authentic standards and surrogate reference materials, the importance of collecting and archiving Total Ion Current MS data, the limitations of using on-line compilations of accurate mass MS data to assign unknown components when multiple isomers are possible, and the often understated magnitude of person-to-person variation that may significantly impact at population level any potential health benefit.
Topics: Humans; Chromatography, Liquid; Tandem Mass Spectrometry; Phenol; Phenols
PubMed: 35489085
DOI: 10.1002/mnfr.202101013 -
Organic Letters Jun 2023A C-N bond-forming cross-dehydrogenative coupling of a collection of Tyr-containing peptides and estrogens with heteroarenes is described. This oxidative coupling is...
A C-N bond-forming cross-dehydrogenative coupling of a collection of Tyr-containing peptides and estrogens with heteroarenes is described. This oxidative coupling is distinguished by its scalability, operational simplicity, and air tolerance and enables the appendance of phenothiazines and phenoxazines in phenol-like compounds. When incorporated into a Tb(III) metallopeptide, the Tyr-phenothiazine moiety acts as a sensitizer for the Tb(III) ion, providing a new tool for the design of luminescent probes.
Topics: Amination; Phenol; Oxidative Coupling; Phenols
PubMed: 37284781
DOI: 10.1021/acs.orglett.3c01560 -
Nutrients Feb 2023The type 2 diabetes epidemic is real and hardly coming to an end in the upcoming years. The efforts of the scientific community to develop safer and more effective...
The type 2 diabetes epidemic is real and hardly coming to an end in the upcoming years. The efforts of the scientific community to develop safer and more effective compounds for type 2 diabetes based on the structure of natural (poly)phenols are remarkable and have indeed proven worthwhile after the introduction of gliflozins in clinical practice. However, low-quality reports on the antidiabetic potential of plant-derived lipophilic (poly)phenols continue to pile up in the literature. Many of these compounds continue to be published as promising functional nutrients and antidiabetic pharmaceutical leads without consideration of their Pan-Assay Interference Compounds (PAINS) profile. This evidence-based opinion article conveys the authors' perspectives on the natural (poly)phenol artillery as a valuable and reliable source of bioactive compounds for diabetes. Ultimately, in light of the already established membrane-perturbing behavior of lipophilic (poly)phenols, together with the multiple benefits that may come with the introduction of a -glucosyl moiety in bioactive compounds, we aim to raise awareness of the importance of contemplating the shift to (poly)phenol-carbohydrate combinations in the development of functional nutrients, as well as in the early stages of antidiabetic drug discovery.
Topics: Humans; Diabetes Mellitus, Type 2; Phenol; Phenols; Hypoglycemic Agents; Carbohydrates
PubMed: 36839354
DOI: 10.3390/nu15040996