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Novel Regioselective Synthesis of Urolithin Glucuronides─Human Gut Microbiota Cometabolites of Ellagitannins and Ellagic Acid.

ABSTRACT: Urolithins (dibenzo-pyran-[b,d]-6 one derivatives) are human gut microbiota metabolites produced from the natural food antioxidant ellagic acid. Urolithins are better absorbed than ellagic acid and demonstrate biological activities that suggest that they are responsible for the health effects observed after consuming ellagitannin- and ellagic acid-containing foods. Urolithins occur in the systemic circulation as glucuronide conjugates following phase II metabolism. These phase II conjugates are essential for testing the urolithin mechanisms of action in human cell line bioassays. Urolithin glucuronides are not commercially available, and their biosynthesis leads to mixtures of regional isomers. This study describes a novel and regioselective synthesis of urolithin A (3,8-dihydroxy urolithin) 3- and 8-glucuronides and isourolithin A (3,9-dihydroxy urolithin) 3- and 9-glucuronides. The metabolites were characterized using ¹H and ¹³C NMR spectroscopy and UV spectrophotometry. The presence of these metabolites in human subjects belonging to different urolithin metabotypes was also investigated.

SUBMITTER: Villalgordo JM

PROVIDER: S-EPMC9121390 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Novel Regioselective Synthesis of Urolithin Glucuronides─Human Gut Microbiota Cometabolites of Ellagitannins and Ellagic Acid.

Villalgordo Jose M JM Trulli Laura L García-Villalba Rocío R García Victor V Althobaiti Yusuf Y Tomás-Barberán Francisco A FA

Journal of agricultural and food chemistry 20220509 19

Urolithins (dibenzo-pyran-[<i>b</i>,<i>d</i>]-6 one derivatives) are human gut microbiota metabolites produced from the natural food antioxidant ellagic acid. Urolithins are better absorbed than ellagic acid and demonstrate biological activities that suggest that they are responsible for the health effects observed after consuming ellagitannin- and ellagic acid-containing foods. Urolithins occur in the systemic circulation as glucuronide conjugates following phase II metabolism. These phase II c ...[more]

PMID: 35533350

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Project description:Numerous studies signify that diets rich in phytochemicals offer many beneficial functions specifically during pathologic conditions, yet their effects are often not uniform due to inter-individual variation. The host indigenous gut microbiota and their modifications of dietary phytochemicals have emerged as factors that greatly influence the efficacy of phytoceutical-based intervention. Here, we investigated the biological activities of one such active microbial metabolite, Urolithin A (UA or 3,8-dihydroxybenzo[c]chromen-6-one), which is derived from the ellagic acid (EA). Our study demonstrates that UA potently inhibits heme peroxidases i.e. myeloperoxidase (MPO) and lactoperoxidase (LPO) when compared to the parent compound EA. In addition, chrome azurol S (CAS) assay suggests that EA, but not UA, is capable of binding to Fe3+, due to its catechol-like structure, although its modest heme peroxidase inhibitory activity is abrogated upon Fe3+-binding. Interestingly, UA-mediated MPO and LPO inhibition can be prevented by innate immune protein human NGAL or its murine ortholog lipocalin 2 (Lcn2), implying the complex nature of host innate immunity-microbiota interactions. Spectral analysis indicates that UA inhibits heme peroxidase-catalyzed reaction by reverting the peroxidase back to its inactive native state. In support of these in vitro results, UA significantly reduced phorbol myristate acetate (PMA)-induced superoxide generation in neutrophils, however, EA failed to block the superoxide generation. Treatment with UA significantly reduced PMA-induced mouse ear edema and MPO activity compared to EA treated mice. Collectively, our results demonstrate that microbiota-mediated conversion of EA to UA is advantageous to both host and microbiota i.e. UA-mediated inhibition of pro-oxidant enzymes reduce tissue inflammation, mitigate non-specific killing of gut bacteria, and abrogate iron-binding property of EA, thus providing a competitive edge to the microbiota in acquiring limiting nutrient iron and thrive in the gut.

Dataset Information

Novel Regioselective Synthesis of Urolithin Glucuronides─Human Gut Microbiota Cometabolites of Ellagitannins and Ellagic Acid.

Publications

Novel Regioselective Synthesis of Urolithin Glucuronides─Human Gut Microbiota Cometabolites of Ellagitannins and Ellagic Acid.

Similar Datasets

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