Stratification of Volunteers According to Flavanone Metabolite Excretion and Phase II Metabolism Profile after Single Doses of ‘Pera’ Orange and ‘Moro’ Blood Orange Juices

Large interindividual variations in the biological response to citrus flavanones have been observed, and this could be associated with high variations in their bioavailability. The aim of this study was to identify the main determinants underlying interindividual differences in citrus flavanone metabolism and excretion. In a randomized cross-over study, non-obese and obese volunteers, aged 19–40 years, ingested single doses of Pera and Moro orange juices, and urine was collected for 24 h. A large difference in the recovery of the urinary flavanone phase II metabolites was observed, with hesperetin-sulfate and hesperetin-sulfo-O-glucuronide being the major metabolites. Subjects were stratified according to their total excretion of flavanone metabolites as high, medium, and low excretors, but the expected correlation with the microbiome was not observed at the genus level. A second stratification was proposed according to phase II flavanone metabolism, whereby participants were divided into two excretion groups: Profiles A and B. Profile B individuals showed greater biotransformation of hesperetin-sulfate to hesperetin-sulfo-O-glucuronide, as well as transformation of flavanone-monoglucuronide to the respective diglucuronides, suggestive of an influence of polymorphisms on UDP-glucuronosyltransferase. In conclusion, this study proposes a new stratification of volunteers based on their metabolic profiles. Gut microbiota composition and polymorphisms of phase II enzymes may be related to the interindividual variability of metabolism.

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

European Journal of Nutrition ◽

10.1007/s00394-020-02386-y ◽

2020 ◽

Author(s):

Aneta Bobowska ◽

Sebastian Granica ◽

Agnieszka Filipek ◽

Matthias F. Melzig ◽

Thomas Moeslinger ◽

...

Keyword(s):

Molecular Weight ◽

Inflammatory Response ◽

Phase Ii ◽

Comparative Studies ◽

Active Metabolite ◽

Phase Ii Metabolism ◽

Urolithin A ◽

Tnf Α ◽

Phase Ii Metabolites

Abstract Purpose Ellagitannins 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. Methods The 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. Results Urolithin 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. Conclusion Comparative 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.

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Contribution of plant food bioactives in promoting health effects of plant foods: why look at interindividual variability?

European Journal of Nutrition ◽

10.1007/s00394-019-02096-0 ◽

2019 ◽

Vol 58 (S2) ◽

pp. 13-19 ◽

Cited By ~ 7

Author(s):

Christine Morand ◽

Francisco A. Tomás-Barberán

Keyword(s):

Health Effects ◽

Interindividual Variability ◽

Food Sources ◽

Cardiometabolic Health ◽

Plant Food ◽

Health It ◽

Plant Foods ◽

Nutritional Needs ◽

Main Determinants ◽

Actual Contribution

Abstract Purpose Research has identified plant-based diets as the most protective for our health; it is now essential to focus on good food associations and the beneficial constituents in plant foods. From a growing body of evidence, some categories of food phytochemicals are increasingly considered to play a crucial role in the cardiometabolic health effects associated with plant food consumption. However, the heterogeneity in responsiveness to plant food bioactive intake that is frequently observed in clinical trials can hinder the identification of the effects of these compounds in specific subpopulations and likely lead to underestimating their actual contribution to the health effects of their food sources. Results The magnitude and the main factors responsible for this between-subject variation in response to the consumption of the major families of food phytochemicals have been poorly documented so far. Thus, research efforts in this area must be developed. More importantly, capturing the interindividual variability in response to plant food bioactive intake, together with identifying the main determinants involved, is a crucial step that will enable the development and production of plant food products, thereby satisfying the nutritional needs and conferring benefits to different categories of populations. Conclusion The development of a science-based personalised nutrition approach focusing on plant foods rich in specific bioactive compounds could contribute to alleviating the dramatic burden of metabolic and cardiovascular diseases.

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Characterization of phase I and phase II metabolites of hop (Humulus lupulus L.) bitter acids: In vitro and in vivo metabolic profiling by UHPLC-Q-Orbitrap

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2021.114107 ◽

2021 ◽

pp. 114107

Author(s):

Emanuela Salviati ◽

Eduardo Sommella ◽

Albino Carrizzo ◽

Veronica Di Sarno ◽

Alessia Bertamino ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Metabolic Profiling ◽

Humulus Lupulus ◽

Humulus Lupulus L ◽

Bitter Acids ◽

Phase Ii Metabolites

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An in vitro study on the transport and phase II metabolism of the mycotoxin alternariol in combination with the structurally related gut microbial metabolite urolithin C

Toxicology Letters ◽

10.1016/j.toxlet.2021.01.007 ◽

2021 ◽

Author(s):

Francesco Crudo ◽

Amelia Barilli ◽

Pedro Mena ◽

Bianca Maria Rotoli ◽

Daniele Del Rio ◽

...

Keyword(s):

Phase Ii ◽

In Vitro Study ◽

Vitro Study ◽

Phase Ii Metabolism ◽

Microbial Metabolite

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Metabolism of anabolic androgenic steroids

Clinical Chemistry ◽

10.1093/clinchem/42.7.1001 ◽

1996 ◽

Vol 42 (7) ◽

pp. 1001-1020 ◽

Cited By ~ 223

Author(s):

W Schänzer

Keyword(s):

Phase I ◽

Physical Performance ◽

Phase Ii ◽

Anabolic Androgenic Steroids ◽

Phase Ii Metabolism ◽

Steroid Molecule ◽

High Extent ◽

As Doping ◽

General Metabolism ◽

Androgenic Steroids

Abstract Anabolic androgenic steroids (AAS) are misused to a high extent in sports by athletes to improve their physical performance. Sports federations consider the use of these drugs in sports as doping. The misuse of AAS is controlled by detection of the parent AAS (when excreted into urine) and (or) their metabolites in urine of athletes. I present a review of the metabolism of AAS. Testosterone is the principal androgenic steroid and its metabolism is compared with that of AAS. The review is divided into two parts: the general metabolism of AAS, which is separated into phase I and phase II metabolism and includes a systematic discussion of metabolic changes in the steroid molecule according to the regions (A-D rings), and the specific metabolism of AAS, which presents the metabolism of 26 AAS in humans.

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Metabolism of (2S)-Pterosin A: Identification of the Phase I and Phase II Metabolites in Rat Urine

Drug Metabolism and Disposition ◽

10.1124/dmd.112.045039 ◽

2012 ◽

Vol 40 (8) ◽

pp. 1566-1574 ◽

Cited By ~ 8

Author(s):

Yung-Ping Lee ◽

Feng-Lin Hsu ◽

Jaw-Jou Kang ◽

Chien-Kuang Chen ◽

Shoei-Sheng Lee

Keyword(s):

Phase I ◽

Phase Ii ◽

Rat Urine ◽

Phase Ii Metabolites

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Microbial production of phase I and phase II metabolites of midazolam

Xenobiotica ◽

10.3109/00498254.2011.622417 ◽

2011 ◽

Vol 42 (3) ◽

pp. 285-293 ◽

Cited By ~ 5

Author(s):

Cyrille Marvalin ◽

Mireille Denoux ◽

Serge Pérard ◽

Sébastien Roy ◽

Robert Azerad

Keyword(s):

Phase I ◽

Phase Ii ◽

Microbial Production ◽

Phase Ii Metabolites

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Phase II pharmaceutical metabolites acetaminophen glucuronide and acetaminophen sulfate in wastewater

Environmental Chemistry ◽

10.1071/en09098 ◽

2010 ◽

Vol 7 (1) ◽

pp. 111 ◽

Cited By ~ 5

Author(s):

Manjula Sunkara ◽

Martha J. M. Wells

Keyword(s):

Surface Water ◽

Phase Ii ◽

Pharmaceutical Compounds ◽

Treatment Result ◽

Secondary Treatment ◽

Uv Treatment ◽

Pharmaceutical Agent ◽

Analytical Protocol ◽

Acetaminophen Glucuronide ◽

Phase Ii Metabolites

Environmental context. Excretion of pharmaceuticals and their metabolites by humans and animals, flushing unused pharmaceuticals and inadequate water treatment result in the occurrence of these chemicals as pollutants in wastewater, surface water and drinking water. In this research, the pharmaceutical agent acetaminophen (paracetamol, Tylenol) and its glucuronide and sulfate metabolites were examined as a model system for monitoring wastewater influent and effluent. The true risk to ecosystems and humans from the occurrence of pharmaceuticals in our water supply can only be estimated if accurate concentrations of parent pharmaceutical chemicals as well as their metabolites are measured. Abstract. An analytical method was developed to separately determine acetaminophen and its Phase II metabolites, acetaminophen glucuronide and acetaminophen sulfate, from wastewater in a single extract. The method developed will serve as a model for screening for the presence of other non-steroidal pharmaceutical compounds and their Phase II metabolites in wastewater. Acetaminophen glucuronide was not present in the wastewater influent tested to verify the analytical protocol, whereas concentrations of acetaminophen and acetaminophen sulfate in the influent were reproducible over time. A Phase I metabolite, p-aminophenol, was also determined to occur in the wastewater influent. Concentrations of the analytes-of-interest, detected in effluent samples collected after secondary treatment, but before UV treatment, were highly variable and were undetectable after UV treatment before release to surface water.

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