Paul A Kroon
Institute of Food Research, Food and Health, Faculty Member
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BackgroundOsteoarthritis (OA) accounts for more than a third of chronic moderate to severe pain in the UK. Sulforaphane (SFN) is a naturally occurring phytochemical derived from eating cruciferous vegetables, particularly broccoli. It has... more
BackgroundOsteoarthritis (OA) accounts for more than a third of chronic moderate to severe pain in the UK. Sulforaphane (SFN) is a naturally occurring phytochemical derived from eating cruciferous vegetables, particularly broccoli. It has several biological activities that promote health, including anti-inflammatory properties. SFN has a potential role in limiting pain and cartilage destruction in OA.ObjectivesIn a two centre, placebo-controlled, double-blind, two-arm parallel, RCT, proof of principle study with a primary outcome we evaluated whether dietary SFN (from consumption of broccoli) improves pain in participants with knee OA. Secondary objectives were to determine whether food containing SFN improves knee function, and the feasibility of the study design for an appropriately powered trial.MethodsParticipants with symptomatic and radiographic knee OA were recruited from regions of Norfolk and Leeds in the UK, were over 50 years of age with moderate to severe knee pain (at l...
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New Findings What is the topic of this review? The role of the gut microbiome in physiology and how it can be targeted as an effective strategy against two of the most important global medical challenges of our time, namely, metabolic... more
New Findings What is the topic of this review? The role of the gut microbiome in physiology and how it can be targeted as an effective strategy against two of the most important global medical challenges of our time, namely, metabolic diseases and antibacterial resistance. What advances does it highlight? The critical roles of the microbiome in regulating host physiology and how microbiome analysis is useful for disease stratification to enable informed clinical decisions and develop interventions such as faecal microbiota transplantation, prebiotics and probiotics. Also, the limitations of microbiome modulation, including the potential for probiotics to enhance antimicrobial resistance gene reservoirs, and that currently a ‘healthy microbiome’ that can be used as a biobank for transplantation is yet to be defined. The human gut microbiome is a key factor in the development of metabolic diseases and antimicrobial resistance, which are among the greatest global medical challenges of ...
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The increased presence of bacteria in blood is a plausible contributing factor in the development and progression of aging-associated diseases. In this context, we performed the quantification and the taxonomic profiling of the bacterial... more
The increased presence of bacteria in blood is a plausible contributing factor in the development and progression of aging-associated diseases. In this context, we performed the quantification and the taxonomic profiling of the bacterial DNA in blood samples collected from forty-three older subjects enrolled in a nursing home. Quantitative PCR targeting the 16S rRNA gene revealed that all samples contained detectable amounts of bacterial DNA with a concentration that varied considerably between subjects. Correlation analyses revealed that the bacterial DNAemia (expressed as concentration of 16S rRNA gene copies in blood) significantly associated with the serum levels of zonulin, a marker of intestinal permeability. This result was confirmed by the analysis of a second set of blood samples collected from the same subjects. 16S rRNA gene profiling revealed that most of the bacterial DNA detected in blood was ascribable to the phylum Proteobacteria with a predominance of the genus Pseu...
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Flavanone metabolites decreased the oxidative biomarkers and this effect might be associated with the anti-apoptotic and antioxidant properties of these compounds as well their ability to prevent mitochondrial and insulin secretion... more
Flavanone metabolites decreased the oxidative biomarkers and this effect might be associated with the anti-apoptotic and antioxidant properties of these compounds as well their ability to prevent mitochondrial and insulin secretion dysfunction.
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Research Interests: Nutrition, Obesity, Environmental Health, Biology, Type 2 Diabetes, and 3 moreMedicine, Disease, and Limiting
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Background During aging, alterations of the intestinal microbial ecosystem can occur contributing to immunosenescence, inflamm-aging and impairment of intestinal barrier function (increased intestinal permeability; IP). In the context of... more
Background During aging, alterations of the intestinal microbial ecosystem can occur contributing to immunosenescence, inflamm-aging and impairment of intestinal barrier function (increased intestinal permeability; IP). In the context of a diet-microbiota-IP axis in older subjects, food bioactives such as polyphenols may play a beneficial modulatory role. Methods MaPLE is a project centered on a randomized, controlled cross-over dietary intervention trial [polyphenol-rich diet (PR-diet) versus control diet (C-diet)] targeted to older people (≥ 60 y) living in a well-controlled setting (i.e. nursing home). The 8-week interventions are separated by an 8-week wash-out period. Three small portions per day of selected polyphenol-rich foods are consumed during intervention in substitution of other comparable products within the C-diet. Biological samples are collected before and after each treatment period to evaluate markers related to IP, inflammation, vascular function, oxidative stres...
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Polyphenols are beneficial for health, but are metabolised after consumption.
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Comunicação oral a convite.Introduction Recommendations for a healthy life-style require the consumption of well-balanced foods preferably rich in biologically-active compounds and fibre. The range of claimed healthy foods and functional... more
Comunicação oral a convite.Introduction Recommendations for a healthy life-style require the consumption of well-balanced foods preferably rich in biologically-active compounds and fibre. The range of claimed healthy foods and functional products is enormous; but their role in health and wellbeing is still largely unclear and incompletely specified. One possible way to substantially improve human health through diet is for active dietary ingredients to modulate normal gut microbiota. Methods The influence of methanol extracts of plants (dill, kale, persimmon, sideritis, pomegranate, and nettle) on intestinal microbial coenoses has been evaluated by detection of quantitative changes of key gut microbes. BALB/c mice were fed orally with diluted extracts in concentrations of 50 mg/mouse daily. Major groups of intestinal microbiota were analysed dynamically on days 1, 3, 7, 14 and 24 by using of classical isolation and identification methods. Results In order to be included in the EuroFIR composition data base, national (Bulgarian, Georgian, Romanian, Russian, Turkish and Ukrainian) traditional foods were prioritised in the first stage of the BaSeFood project and indexed according to the LanguaL system. The nutritional content of their macro- and microelements, vitamins and folate were determined [1-4]. The presence in these prioritised dishes and beverages and their major plant components of beneficial and potentially-pathogenic microbes, and foodborne pathogens were investigated [5]. In parallel a study was conducted to determine whether plants ingredients from national traditional foods are able to stimulate the commensal microbes in vivo and to inhibit potentially pathogenic strains [6-7]. Using the mouse model it could be shown that extract of dill inhibits both Enterococcus strains – E. faecalis and E. faecium, Klebsiella pneumoniae and Lactobacillus spp. and stimulates Bifidobacterium bifidum. A similar effect on bifidobacteria was observed after oral administration of kale but in this case an effect on all the other tested representatives of gut microbiota was not detected or was statistically insignificant. On day 3 nettle extract caused an unspecific stimulation of all the tested gut microbiota representatives, but on days 14 and 24 all the indices were approximately equal to their initial levels (for E. coli and K. pneumoniae), but lactobacilli and bifidobacteria were each dramatically reduced. Persimmon was the only extract able to specifically stimulate lactobacilli, and extract of pomegranate acts similarly for bifidobacteria. Extract of sideritis effectively inhibited K. pneumoniae but also commensal E. coli, leading in parallel to a statistically significant increase of bifidobacteria and a not substantially increase of lactobacilli. Discussion Plant components of traditional foods and fermented products are rich sources of beneficial bacteria [8]; these bacteria are present in plant ingredients or fermented products and can be used as potential sources of new probiotic strains. Plants are able to specifically modulate gut microbiota in a manner that is similar to prebiotics – even according to their definition they should not be digested by mammalian host. Conclusion It has been demonstrated that major plant components of traditional Black Sea regional foods can modulate the gut microbiome.This work is funded under the EU FP7 Theme 2: “Food, Agriculture, Fisheries, and Biotechnology”, Grant Agreement no.22711
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... Bioavailability of phytochemicals, such as polyphenols and glucosinolates, was determined from the post-absorptive appearance and disappearance of these compounds and their metabolites in plasma and/or urine after the consumption of... more
... Bioavailability of phytochemicals, such as polyphenols and glucosinolates, was determined from the post-absorptive appearance and disappearance of these compounds and their metabolites in plasma and/or urine after the consumption of plant foods. ...
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Background and PurposeAnthocyanins are phytochemicals with reported vasoactive bioactivity. However, given their instability at neutral pH, they are presumed to undergo significant degradation and subsequent biotransformation. The aim of... more
Background and PurposeAnthocyanins are phytochemicals with reported vasoactive bioactivity. However, given their instability at neutral pH, they are presumed to undergo significant degradation and subsequent biotransformation. The aim of the present study was to establish the pharmacokinetics of the metabolites of cyanidin‐3‐glucoside (C3G), a widely consumed dietary phytochemical with potential cardioprotective properties.Experimental ApproachA 500 mg oral bolus dose of 6,8,10,3′,5′‐13C5‐C3G was fed to eight healthy male participants, followed by a 48 h collection (0, 0.5, 1, 2, 4, 6, 24, 48 h) of blood, urine and faecal samples. Samples were analysed by HPLC‐ESI‐MS/MS with elimination kinetics established using non‐compartmental pharmacokinetic modelling.Key ResultsSeventeen 13C‐labelled compounds were identified in the serum, including 13C5‐C3G, its degradation products, protocatechuic acid (PCA) and phloroglucinaldehyde (PGA), 13 metabolites of PCA and 1 metabolite derived from ...
Research Interests: Pharmacology, Chemistry, Pharmacokinetics, Adolescent, Medicine, and 15 moreHumans, Male, Young Adult, Tandem Mass Spectrometry, Urine, Anthocyanins, High Pressure Liquid Chromatography, Middle Aged, Liquid Chromatography / Electrospray Ionization Mass Spectrometry, Adult, Time Factors, Hippuric Acid, Metabolite, Pharmacology and pharmaceutical sciences, and Cmax
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... WR McLauchlan 1, RH Flatman 1, AI Sancho 1, J. Kakuta 1, CB Faulds 1, GO Elliot 1, PA Kroon 1, CSM Furniss 1, N ... No convincing explanation had been proposed to explain this phenomenon, until 1989, when in a then confidential... more
... WR McLauchlan 1, RH Flatman 1, AI Sancho 1, J. Kakuta 1, CB Faulds 1, GO Elliot 1, PA Kroon 1, CSM Furniss 1, N ... No convincing explanation had been proposed to explain this phenomenon, until 1989, when in a then confidential project, a group led by Professor Jan Maat at ...
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Research Interests: Biochemistry, Chemistry, Nutrition and Dietetics, Food Science, Molecular Biology, and 15 moreClinical Biochemistry, Medicine, In Vitro, Polyphenols, Apples, Nutritional Biochemistry, Glucose Transport, Randomized Controlled Trial, Food Sciences, Meal, Polyphenol, Carbohydrate, Biochemistry and cell biology, Postprandial Lipemia, and Phlorizin
SCOPE Dietary polyphenols can alter the gut microbiota (GM) and promote the production of bioactive metabolites. Several indoles result of GM metabolism of dietary tryptophan have been associated with intestinal barrier integrity. Our aim... more
SCOPE Dietary polyphenols can alter the gut microbiota (GM) and promote the production of bioactive metabolites. Several indoles result of GM metabolism of dietary tryptophan have been associated with intestinal barrier integrity. Our aim was to study the changes in GM-derived indoles during a polyphenol-rich (PR) diet intervention in older adults. METHODS AND RESULTS Randomized, controlled, crossover trial in adults ≥60y living in a residential care facility during an 8-week PR versus control diet (n = 51). Seven GM-tryptophan metabolites were measured in serum, and metataxonomic analysis of GM was performed on fecal samples. Exploratory subgroup analyses were performed based on renal function (RF). The PR-diet significantly increased serum IPA in subjects with normal RF, but not in subjects with impaired RF. Other GM-tryptophan metabolites were not affected. Comparison of baseline GM composition showed shifts in Bacteroidales order members as well as higher abundance of Clostridiales in participants with normal RF. During the trial, variations of IPA were associated with changes in C-reactive protein (β = 0.32, p = 0.010) and GM, particularly with the Clostridiales (r = 0.35, p<0.001) and Enterobacteriales (r = -0.15, p<0.05) orders. CONCLUSION A PR diet increases the serum concentration of IPA in older adults with normal RF. Our findings may be important when defining appropriate dietary interventions for older adults. TRIAL REGISTRATION NUMBER ISRCTN10214981 (https://doi.org/10.1186/ISRCTN10214981). This article is protected by copyright. All rights reserved.
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Research Interests: Pharmacology, Chemistry, British, Medicine, Animals, and 15 moreQuercetin, Flavonoid, Pyrazoles, Sus Scrofa, Forskolin, Drug Tolerance, cyclic GMP, Nitroglycerin, Sodium Nitroprusside, Bradykinin, Coronary artery, Arteries, nitroprusside, Pharmacology and pharmaceutical sciences, and Coronary Vessels
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Junctional adhesion molecules (JAMs; comprising JAM-A, -B and -C) act as receptors for viruses, mediate cell permeability, facilitate leukocyte migration during sterile and non-sterile inflammation and are important for the maintenance of... more
Junctional adhesion molecules (JAMs; comprising JAM-A, -B and -C) act as receptors for viruses, mediate cell permeability, facilitate leukocyte migration during sterile and non-sterile inflammation and are important for the maintenance of epithelial barrier integrity. As such, they are implicated in the development of both communicable and non-communicable chronic diseases. Here, we investigated the expression and regulation of JAM-B in leukocytes under pathogen- and host-derived inflammatory stimuli using immunoassays, qPCR and pharmacological inhibitors of inflammatory signalling pathways. We show that JAM-B is expressed at both the mRNA and protein level in leukocytes. JAM-B protein is localised to the cytoplasm, Golgi apparatus and in the nucleus around ring-shaped structures. We also provide evidence that JAM-B nuclear localisation occurs via the classical importin-α/β pathway, which is likely mediated through JAM-B protein nuclear localisation signals (NLS) and export signals ...
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The evaluation of food intake in older subjects is crucial in order to be able to verify adherence to nutritional recommendations. In this context, estimation of the intake of specific dietary bioactives, such as polyphenols, although... more
The evaluation of food intake in older subjects is crucial in order to be able to verify adherence to nutritional recommendations. In this context, estimation of the intake of specific dietary bioactives, such as polyphenols, although particularly challenging, is necessary to plan possible intervention strategies to increase their intake. The aims of the present study were to: (i) evaluate the nutritional composition of dietary menus provided in a residential care setting; (ii) estimate the actual intake of nutrients and polyphenols in a group of older subjects participating in the MaPLE study; and (iii) investigate the impact of an eight-week polyphenol-rich dietary pattern, compared to an eight-week control diet, on overall nutrient and polyphenol intake in older participants. The menus served to the participants provided ~770 mg per day of total polyphenols on average with small variations between seasons. The analysis of real consumption, measured using weighed food diaries, dem...
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The use of DNA damage as marker of oxidative stress, metabolic dysfunction and age-related diseases is debated. The present study aimed at assessing the level of DNA damage (evaluated as DNA strand-breaks, endogenous and... more
The use of DNA damage as marker of oxidative stress, metabolic dysfunction and age-related diseases is debated. The present study aimed at assessing the level of DNA damage (evaluated as DNA strand-breaks, endogenous and oxidatively-induced DNA damage) in a group of older subjects with intestinal permeability enrolled within the MaPLE (Gut and Blood Microbiomics for Studying the Effect of a Polyphenol-Rich Dietary Pattern on Intestinal Permeability in the Elderly) intervention trial, to evaluate its association with clinical, metabolic and dietary markers. DNA damage in peripheral blood mononuclear cells was assessed by the comet assay in 49 older subjects participating in the study. Clinical and metabolic markers, markers of inflammation, vascular function and intestinal permeability were determined in serum. Food intake was estimated by weighted food diaries. On the whole, a trend towards higher levels of DNA damage was observed in men compared to women (p = 0.071). A positive ass...
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Aging can be characterized by increased systemic low-grade inflammation, altered gut microbiota composition, and increased intestinal permeability (IP). The intake of polyphenol-rich foods is proposed as a promising strategy to positively... more
Aging can be characterized by increased systemic low-grade inflammation, altered gut microbiota composition, and increased intestinal permeability (IP). The intake of polyphenol-rich foods is proposed as a promising strategy to positively affect the gut microbiota–immune system–intestinal barrier (IB) axis. In this context, we tested the hypothesis that a PR-dietary intervention would affect the presence of bacterial factors in the bloodstream of older adults. We collected blood samples within a randomized, controlled, crossover intervention trial in which older volunteers (n = 51) received a polyphenol-enriched and a control diet. We quantified the presence of bacterial DNA in blood by qPCR targeting the 16S rRNA gene (16S; bacterial DNAemia). Blood DNA was taxonomically profiled via 16S sequencing. Higher blood 16S levels were associated with higher BMI and markers of IP, inflammation, and dyslipidemia. PR-intervention did not significantly change bacterial DNAemia in the older population (P = 0.103). Nonetheless, the beneficial changes caused by the polyphenol-enriched diet were greatest in participants with higher bacterial DNAemia, specifically in markers related to IP, inflammation and dyslipidemia, and in fecal bacterial taxa. Finally, we found that the bacterial DNA detected in blood mostly belonged to γ-Proteobacteria, whose abundance significantly decreased after the polyphenol-rich diet in subjects with higher bacterial DNAemia at baseline. This study shows that older subjects with higher bacterial DNAemia experienced a beneficial effect from a polyphenol-rich diet. Bacterial DNAemia may be a further relevant marker for the identification of target populations that could benefit more from a protective dietary treatment. This trial was retrospectively registered at www.isrctn.org (ISRCTN10214981) on April 28, 2017.
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The gut microbiota is critical to the maintenance of physiological homeostasis and as such is implicated in a range of diseases such as colon cancer, ulcerative colitis, diabetes, cardiovascular diseases, and neurodegenerative diseases.... more
The gut microbiota is critical to the maintenance of physiological homeostasis and as such is implicated in a range of diseases such as colon cancer, ulcerative colitis, diabetes, cardiovascular diseases, and neurodegenerative diseases. Short chain fatty acids (SCFAs) are key metabolites produced by the gut microbiota from the fermentation of dietary fibre. Here we present a novel, sensitive, and direct LC-MS/MS technique using isotopically labelled internal standards without derivatisation for the analysis of SCFAs in different biological matrices. The technique has significant advantages over the current widely used techniques based on sample derivatization and GC-MS analysis, including fast and simple sample preparation and short LC runtime (10 min). The technique is specific and sensitive for the quantification of acetate, butyrate, isobutyrate, isovalerate, lactate, propionate and valerate. The limits of detection were all 0.001 mM except for acetate which was 0.003 mM. The cal...
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Urinary polyphenol metabolites are potential biomarkers of dietary polyphenol intake. The current study aims to evaluate associations between total diet, vegetable and fruit polyphenol intakes with urinary polyphenol metabolite... more
Urinary polyphenol metabolites are potential biomarkers of dietary polyphenol intake. The current study aims to evaluate associations between total diet, vegetable and fruit polyphenol intakes with urinary polyphenol metabolite concentrations in a sample of adults prescribed a diet rich in vegetables and fruit. Thirty-four participants completed a 10-week pre-post study. Participants were asked to consume Australian recommended daily vegetable and fruit serves and attend measurement sessions at baseline and at weeks 2 and 10. Two 24-h diet recalls were collected at each time-point and polyphenol intakes were calculated using the Phenol-Explorer database. Spot urine samples, collected at each time-point, were analyzed for 15 polyphenol metabolites using liquid chromatography-mass spectroscopy. Spearman’s correlation analyzes assessed the strength of relationships between urinary and dietary polyphenols. Linear mixed models were used to investigate relationships between polyphenol exc...
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Growing evidence support association between polyphenol intake and reduced risk for chronic diseases, even if there is a broad debate about the effective amount of polyphenols able to exert such protective effect. The present systematic... more
Growing evidence support association between polyphenol intake and reduced risk for chronic diseases, even if there is a broad debate about the effective amount of polyphenols able to exert such protective effect. The present systematic review provides an overview of the last 10-year literature on the evaluation of polyphenol intake and its association with specific disease markers and/or endpoints. An estimation of the mean total polyphenol intake has been performed despite the large heterogeneity of data reviewed. In addition, the contribution of dietary sources was considered, suggesting tea, coffee, red wine, fruit and vegetables as the main products providing polyphenols. Total flavonoids and specific subclasses, but not total polyphenols, have been apparently associated with a low risk of diabetes, cardiovascular events and all-cause mortality. However, large variability in terms of methods for the evaluation and quantification of polyphenol intake, markers and endpoints consi...
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The inevitable rise of the proportion of people aged [...]
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A fluorescence-based enzymatic microplate intracellular glucose assay was designed and fully validated. The method was tested in a hepatocellular cancer cell line (HepG2). Our novel one-step extraction reagent gave stable cell lysates for... more
A fluorescence-based enzymatic microplate intracellular glucose assay was designed and fully validated. The method was tested in a hepatocellular cancer cell line (HepG2). Our novel one-step extraction reagent gave stable cell lysates for glucose, adenosine triphosphate (ATP), and total protein determination from the same sample. Limit of detection for glucose was 0.13 µM (26 pmol/well), which is superior to commercially available glucose assays. Both intra- and interday assay imprecision in HepG2 cultures were less than 12% coefficient of variance (CV). In cell lysates spiked with glucose, recovery at two levels varied between 83.70% and 91.81%, and both linearity and stability were acceptable. HepG2 cells treated with agents affecting glucose uptake/metabolism (phloretin, quercetin, quercetin-3′-sulfate, NaF, 3-bromopyruvate, NaN3, oligomycin A, ochratoxin A, cytochalasin B, and anti-GLUT1 antibody) showed dose-dependent changes in glucose and ATP levels without total protein (cel...
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Understanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to... more
Understanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, w...
Research Interests: Genetics, Food Science, Biomarkers, Food, Biology, and 15 moreDiet, Medicine, Energy Metabolism, Humans, Dietary Supplements, Meta Analysis, Anthocyanins, Molecular sciences, Cardiovascular system, Myocardium, Berries, Cardiovascular Diseases, Ellagitannins, Anthocyanin, and Interindividual Variability
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... more
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, 27.6, and 73.2 μM, respectively, and their anticancer effect was ranked as Que > Q3'S > Q3G. Furthermore, flow cytometric assay revealed that Que, Q3'S, and Q3G mediated the cell-cycle arrest principally at the S phase and decreased the number of G0/G1 and G2/M after a 48 h treatment with human breast MCF-7 cells. Moreover, it was found that 70.8%, 58.2%, and 48.0% of MCF-7 cancer cells entered the early phase of apoptosis when treated with 100 μM Que, Q3'S, and Q3G for 48 h, respectively. In addition, induction of apoptosis by Que, Q3&...
Research Interests: Chemistry, Apoptosis, Medicine, Cancer Cell, Quercetin, and 4 moreFood Sciences, Mcf, Intracellular, and Food Function
We have studied the uptake of quercetin aglycone into CaCo-2/TC7 cells in the presence and absence of mixed micelles that are present in the human small intestine. The micelles inhibited the transport of quercetin into the cells. To gain... more
We have studied the uptake of quercetin aglycone into CaCo-2/TC7 cells in the presence and absence of mixed micelles that are present in the human small intestine. The micelles inhibited the transport of quercetin into the cells. To gain an understanding of why this is the case we examined the solubilisation of quercetin in micelles of differing composition and into pure lipid phases. We did this by using the environmental sensitivity of quercetin's UV-visible absorption spectra and measurement of free quercetin by filtration of the micellar solutions. The nature of the micelles was also studied by pyrene fluorescence. We found that the partitioning of quercetin into simple bile salt micelles was low and for mixed micelles was inhibited by increasing the bile salt concentration. The affinity of quercetin decreased in the order egg phosphatidylcholine (PC) = lysoPC > mixed micelles > bile salts. These results, together with the innate properties of quercetin, contribute to ...
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Research Interests: Chemistry, Drug metabolism, Medicine, Humans, Cyclosporine, and 14 moreMembrane transport proteins, High Pressure Liquid Chromatography, Caco-2 cells, Quercetin, Protein Conformation, Amino Acid Sequence, Quinolines, Recombinant Proteins, Protein Binding, Molecular Structure, Molecular Sequence Data, Cell Membrane, Pharmacology and pharmaceutical sciences, and stereoisomerism
To understand the bioaccessibility of the flavonoid quercetin we studied its interaction with bile salt micelles. The environmental sensitivity of quercetin's UV-visible absorption spectrum gave information about quercetin... more
To understand the bioaccessibility of the flavonoid quercetin we studied its interaction with bile salt micelles. The environmental sensitivity of quercetin's UV-visible absorption spectrum gave information about quercetin partitioning. Two quercetin absorption peaks gave complementary information: Peak A (240-280nm) on the intermicellar phase and Peak B (340-440nm) on the micellar phase. Thus, by altering pH, we showed that only non-ionised quercetin partitions into micelles. We validated our interpretation by studying quercetin's interaction with SDS micelles. Pyrene fluorescence and the quercetin UV-visible spectra show that the adsorption site for pyrene and quercetin in bile salt micelles is more hydrophobic than that for SDS micelles. Also, both quercetin and pyrene reported a higher critical micelle concentration for bile salts than for SDS. Our method of using a flavonoid as an intrinsic probe, is generally applicable to other lipophilic bioactives, whenever they hav...
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Purpose Plasma trimethylamine-N-oxide (TMAO) levels have been shown to correlate with increased risk of metabolic diseases including cardiovascular diseases. TMAO exposure predominantly occurs as a consequence of gut microbiota-dependent... more
Purpose Plasma trimethylamine-N-oxide (TMAO) levels have been shown to correlate with increased risk of metabolic diseases including cardiovascular diseases. TMAO exposure predominantly occurs as a consequence of gut microbiota-dependent trimethylamine (TMA) production from dietary substrates including choline, carnitine and betaine, which is then converted to TMAO in the liver. Reducing microbial TMA production is likely to be the most effective and sustainable approach to overcoming TMAO burden in humans. Current models for studying microbial TMA production have numerous weaknesses including the cost and length of human studies, differences in TMA(O) metabolism in animal models and the risk of failing to replicate multi-enzyme/multi-strain pathways when using isolated bacterial strains. The purpose of this research was to investigate TMA production from dietary precursors in an in-vitro model of the human colon. Methods TMA production from choline, l-carnitine, betaine and γ-butyr...
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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.... more
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. However, the interactions of its metabolites with biotransformation enzymes and drug transporters have barely been examined. In this study, the inhibitory effects of quercetin and its most relevant methyl, sulfate, and glucuronide metabolites were tested on cytochrome P450 (CYP) (2C19, 3A4, and 2D6) enzymes as well as on organic anion-transporting polypeptides (OATPs) (OATP1A2, OATP1B1, OATP1B3, and OATP2B1) and ATP (adenosine triphosphate) Binding Cassette (ABC) (BCRP and MRP2) transporters. Quercetin and its metabolites (quercetin-3′-sulfate, quercetin-3-glucuronide, isorhamnetin, and isorhamnetin-3-glucuronide) showed weak inhibi...
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Isoflavones and isoflavandiols have shown many health benefits, such as reducing cardiovascular disease, cancer, age-related disease, and osteoporosis. However, to investigate the relationships between consumption of isoflavones and their... more
Isoflavones and isoflavandiols have shown many health benefits, such as reducing cardiovascular disease, cancer, age-related disease, and osteoporosis. However, to investigate the relationships between consumption of isoflavones and their health benefits, it is important to be able to accurately quantify exposure in the large numbers of samples typically produced in association studies (i.e., several thousands). Current methods rely on solid-phase extraction protocols for sample cleanup, resulting in protracted extraction and analysis times. Here, we describe a fast and easy sample preparation method of human urine samples for subsequent quantification of daidzein, genistein (isoflavones), and equol (isoflavandiol) using LC-MS/MS. Sample preparation involves only the addition of dimethylformamide (DMF) and formic acid (FA) after enzymatic hydrolysis of their metabolites by a β-glucuronidase and sulfatase mixture. The method was validated by precision, linearity, accuracy, recoveries...
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... more
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. Reported data from randomized controlled trials have shown that anthocyanin consumption increased PON1 activity. However, the underlying molecular mechanisms by which anthocyanins increase PON1 activity are not understood. Therefore, the aim of this research was to investigate the ability of anthocyanins and their metabolites to increase PON1 gene expression and/or enzyme activities as potential mechanisms. The effect of the two predominant dietary anthocyanins and 18 of their recently identified microbial metabolites including their phase-II conjugates on PO...