The 2-aminoethyl diphenylborinate-based fluorescent method identifies quercetin and luteolin metabolites as substrates of Organic anion transporting polypeptides, OATP1B1 and OATP2B1.

Organic anion transporting polypeptides (OATPs), OATP1B1 and OATP2B1 are membrane proteins mediating the cellular uptake of chemically diverse organic compounds. OATP1B1 is exclusively expressed in hepatocytes and plays a key role in hepatic detoxification. The ubiquitously expressed OATP2B1 promotes the intestinal absorption of orally administered drugs.

Association of Outpatient Behavioral Health Treatment With Medical and Pharmacy Costs in the First 27 Months Following a New Behavioral Health Diagnosis in the US.

Importance: Outpatient behavioral health treatment (OPBHT) is an effective treatment for behavioral health conditions (BHCs) that may also be associated with improved medical health outcomes, but evidence regarding the cost-effectiveness of OPBHT across a large population has not been established.

Objective: To investigate whether individuals newly diagnosed with a BHC who used OPBHT incurred lower medical and pharmacy costs over 15 and 27 months of follow-up compared with those not using OPBHT.

Design, Setting, And Participants: This retrospective cohort study of commercially insured individuals in the US was conducted using administrative insurance claims data for individuals newly diagnosed with 1 or more BHCs between January 1, 2017, and December 31, 2018.

Cost Burden Impacts Cancer Patient Service Utilization Behavior in a US Commercial Plan.

The burden of affording high-cost medical treatment (eg, cancer therapy) may impact whether some patients choose to access other needed health services within US commercial plans. However, deferring needed care for a mental or behavioral health (M/BH) condition could result in preventable hospital utilization. This research investigates how income level and total out-of-pocket costs (OOPC) interact to influence the service utilization behavior of insured adult cancer patients with a comorbid M/BH diagnosis.

Anti-Inflammatory Effects of Quercetin on High-Glucose and Pro-Inflammatory Cytokine Challenged Vascular Endothelial Cell Metabolism.

Scope: Pro-inflammatory stimuli such as hyperglycemia and cytokines have been shown to negatively affect endothelial cell functions. The aim of this study is to assess the potential of quercetin and its human metabolites to overcome the deleterious effects of hyperglycemic or inflammatory conditions on the vascular endothelium by modulating endothelial cell metabolism.

Methods And Results: A metabolomics approach enabled identification and quantification of 27 human umbilical vein endothelial cell (HUVEC) metabolites.

Citrus flavanone metabolites protect pancreatic-β cells under oxidative stress induced by cholesterol.

Cholesterol is one of the triggers of oxidative stress in the pancreatic-β cell, generating high levels of reactive oxygen species, which leads to impairment of insulin synthesis and secretion. Bioactive compounds, such as citrus flavanones, which possess anti-inflammatory and antioxidant activities, could reduce oxidative stress in β-cells and improve their function. We describe for the first time the protective effects of the phase-II flavanone metabolites [naringenin 7-O-glucuronide, hesperetin 3'-O-glucuronide, and hesperetin 7-O-glucuronide], and two flavanones-catabolites derived from gut microbiota metabolism [hippuric acid and 3-(4-hydroxyphenyl)propionic acid], on pancreatic β-cell line MIN6 under oxidative stress, at physiologically relevant concentration.

Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters.

Quercetin is a flavonoid, its glycosides and aglycone are found in significant amounts in several plants and dietary supplements. Because of the high presystemic biotransformation of quercetin, mainly its conjugates appear in circulation. As has been reported in previous studies, quercetin can interact with several proteins of pharmacokinetic importance.

Monomeric Flavanols Are More Efficient Substrates for Gut Microbiota Conversion to Hydroxyphenyl-γ-Valerolactone Metabolites Than Oligomeric Procyanidins: A Randomized, Placebo-Controlled Human Intervention Trial.

Scope: The majority of ingested flavanols reach the colon where they are catabolized by the microbiota to form hydroxyphenyl-γ-valerolactones (HGVLs). It is not known if the HGVLs are catabolic products of monomeric (epi)catechins (EPC), oligomeric procyanidins (OPCs), or both. Using data from a randomized, double-blind, placebo-controlled crossover trial the relative contributions of catechins and OPC to the bioavailable pool of HGVLs are estimated.

The Effects of Anthocyanins and Their Microbial Metabolites on the Expression and Enzyme Activities of Paraoxonase 1, an Important Marker of HDL Function.

High circulating HDL concentrations and measures of various HDL functions are inversely associated with cardiovascular disease (CVD) risk. Paraoxonase 1 (PON1) contributes to many of the athero-protective functions of HDL, such as promoting the reverse cholesterol transport process and reducing the levels of oxidized LDL. PON1 activities are influenced by several factors, the most important being diet and genetic polymorphisms.

Plant Bioactives and the Prevention of Prostate Cancer: Evidence from Human Studies.

Prostate cancer has become the most common form of non-cutaneous (internal) malignancy in men, accounting for 26% of all new male visceral cancer cases in the UK. The aetiology and pathogenesis of prostate cancer are not understood, but given the age-adjusted geographical variations in prostate cancer incidence quoted in epidemiological studies, there is increasing interest in nutrition as a relevant factor. In particular, foods rich in phytochemicals have been proposed to reduce the risk of prostate cancer.

Accumulation of Dietary S-Methyl Cysteine Sulfoxide in Human Prostate Tissue.

Scope: Observational studies have associated consumption of cruciferous vegetables with reduced risk of prostate cancer. This effect has been associated with the degradation products of glucosinolates-thioglycosides that accumulate within crucifers. The possible role of S-methyl cysteine sulfoxide, a metabolite that also accumulates in cruciferous vegetables, and its derivatives, in cancer prevention is relatively unexplored compared to glucosinolate derivatives.

Hydrophobic Interactions Drive Binding between Vascular Endothelial Growth Factor-A (VEGFA) and Polyphenolic Inhibitors.

Some polyphenols have been shown to inhibit, at physiological levels, the VEGF-induced VEGF receptor-2 signaling that causes angiogenesis, allegedly by direct interaction with VEGF and reducing the binding to its receptor VEGFR2. Surface plasmon resonance was used to measure the parameters of binding between VEGF and polyphenols as well as the nature of the interactions by assessing the effect of physico-chemical changes in the solution. CD spectrometry was used to determine any change in the secondary structure of the protein upon binding.

An LC-MS/MS Method to Measure -Methyl-l-Cysteine and -Methyl-l-Cysteine Sulfoxide in Human Specimens Using Isotope Labelled Internal Standards.

This is the first report describing an analytical method for quantitative analysis of two naturally occurring sulphur compounds, -methyl-l-cysteine (SMC) and -methyl-l-cysteine sulfoxide (SMCSO), in human body fluids using isotope-labelled internal standards and liquid chromatography-mass spectrometry (LC-MS)/MS techniques. This method was validated according to the guideline of the Royal Society of Chemistry Analytical Methods Committee. It offers significant advantages including simple and fast preparation of human biological samples.

Correction: Different antitumor effects of quercetin, quercetin-3'-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells.

Correction for 'Different antitumor effects of quercetin, quercetin-3'-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells' by Qiu Wu et al., Food Funct., 2018, 9, 1736-1746.

Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme.

Quercetin is an abundant flavonoid in nature and is used in several dietary supplements. Although quercetin is extensively metabolized by human enzymes and the colonic microflora, we have only few data regarding the pharmacokinetic interactions of its metabolites. Therefore, we investigated the interaction of human and microbial metabolites of quercetin with the xanthine oxidase enzyme.

Psychotherapy and psychopharmacology utilization following repetitive transcranial magnetic stimulation (rTMS) in patients with major depressive disorder.

Lifetime prevalence of major depressive disorder (MDD) among a sample of adults in the United States has been reported as over 16%. Repetitive transcranial magnetic stimulation (rTMS) has become a treatment option for a subset of treatment-refractory patients with MDD. In a population of 159 commercial health plan individuals, we used claims data to compare utilization of antidepressants, antipsychotics, and psychotherapy during the one-year time period prior to rTMS initiation to the one-year time period starting 60 days after rTMS initiation.

Transcriptional changes in prostate of men on active surveillance after a 12-mo glucoraphanin-rich broccoli intervention-results from the Effect of Sulforaphane on prostate CAncer PrEvention (ESCAPE) randomized controlled trial.

Background: Epidemiological evidence suggests that consumption of cruciferous vegetables is associated with reduced risk of prostate cancer progression, largely attributed to the biological activity of glucosinolate degradation products, such as sulforaphane derived from glucoraphanin. Because there are few therapeutic interventions for men on active surveillance for prostate cancer to reduce the risk of cancer progression, dietary approaches are an appealing option for patients.

Objective: We evaluated whether consumption of a glucoraphanin-rich broccoli soup for 1 y leads to changes in gene expression in prostate tissue of men with localized prostate cancer.

Quantitative Dietary Fingerprinting (QDF)-A Novel Tool for Comprehensive Dietary Assessment Based on Urinary Nutrimetabolomics.

Accurate dietary assessment is a challenge in nutritional research, needing powerful and robust tools for reliable measurement of food intake biomarkers. In this work, we have developed a novel quantitative dietary fingerprinting (QDF) approach, which enables for the first time the simultaneous quantitation of about 350 urinary food-derived metabolites, including (poly)phenolic aglycones, phase II metabolites, and microbial-transformed compounds, as well as other compounds (e.g.

Differential Effects of Quercetin and Two of Its Derivatives, Isorhamnetin and Isorhamnetin-3-glucuronide, in Inhibiting the Proliferation of Human Breast-Cancer MCF-7 Cells.

Quercetin (Que) has consistently been reported to be useful cytotoxic compound in vivo and in vitro, but little is known on its metabolites. Here, we examined and compared the cytotoxic effects of Que and its water-soluble metabolites, isorhamnetin (IS) and isorhamnetin-3-glucuronide (I3G), in human breast-cancer MCF-7 cells to uncover their tumor-inhibitory mechanisms and structure-function relationships. The results showed that Que, IS, and I3G could dose-dependently inhibit the growth of MCF-7 cells, and the cytotoxic effect was ranked as Que > IS > I3G.

Different antitumor effects of quercetin, quercetin-3'-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells.

This study was designed to investigate the tumor-inhibitory effects of quercetin (Que) and its water-soluble metabolites, quercetin-3'-sulfate (Q3'S) and quercetin-3-glucuronide (Q3G), as well as to make the molecular mechanism and structure-antitumor relationship clear. It was found that Que, Q3'S, and Q3G could inhibit the growth of human breast cancer MCF-7 cells in a dose-dependent manner, with the IC values of 23.1, 27.

Bioavailability of Glucoraphanin and Sulforaphane from High-Glucoraphanin Broccoli.

Scope: Broccoli accumulates 4-methylsulphinylbutyl glucosinolate (glucoraphanin) which is hydrolyzed to the isothiocyanate sulforaphane. Through the introgression of novel alleles of the Myb28 transcription factor from Brassica villosa, broccoli genotypes have been developed that have enhanced levels of glucoraphanin. This study seeks to quantify the exposure of human tissues to glucoraphanin and sulforaphane following consumption of broccoli with contrasting Myb28 genotypes.

Contribution of the Glucosinolate Fraction to the Overall Antioxidant Potential, Cytoprotection against Oxidative Insult and Antimicrobial Activity of Mill. Leaves Extract.

Background: Mill. (Brassicaceae) is commonly utilized as an ingredient in salads and also as a folk remedy to treat various diseases.

Objective: The objective of this study was to establish the contribution of the glucosinolate (GLS) fraction to the overall antioxidant, cytoprotection against oxidative insult and antimicrobial properties of the hydro-alcoholic extract of leaves from Sicily (Italy), characterized phytochemically.

Vasorelaxant activity of twenty-one physiologically relevant (poly)phenolic metabolites on isolated mouse arteries.

Polyphenols are beneficial for health, but are metabolised after consumption. We compared the vasorelaxant capacity of twenty-one physiologically relevant polyphenol metabolites in isolated mouse arteries. Hesperetin, urolithins and ferulic acid-4-O-sulfate - not their glucuronidated forms or ferulic acid - caused vasorelaxation.

Development, validation and evaluation of an analytical method for the determination of monomeric and oligomeric procyanidins in apple extracts.

There is a lack of data for individual oligomeric procyanidins in apples and apple extracts. Our aim was to develop, validate and evaluate an analytical method for the separation, identification and quantification of monomeric and oligomeric flavanols in apple extracts. To achieve this, we prepared two types of flavanol extracts from freeze-dried apples; one was an epicatechin-rich extract containing ∼30% (w/w) monomeric (-)-epicatechin which also contained oligomeric procyanidins (Extract A), the second was an oligomeric procyanidin-rich extract depleted of epicatechin (Extract B).

Interaction of quercetin and its metabolites with warfarin: Displacement of warfarin from serum albumin and inhibition of CYP2C9 enzyme.

Flavonoids are ubiquitous molecules in nature with manifold pharmacological effects. Flavonoids interact with several proteins, and thus potentially interfere with the pharmacokinetics of various drugs. Though much is known about the protein binding characteristics of flavonoid aglycones, the behaviour of their metabolites, which are extensively formed in the human body has received little attention.