scholarly journals Urolithins: Diet-Derived Bioavailable Metabolites to Tackle Diabetes

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4285
Author(s):  
Ana F. Raimundo ◽  
Sofia Ferreira ◽  
Francisco A. Tomás-Barberán ◽  
Claudia N. Santos ◽  
Regina Menezes
Keyword(s):  
Molecular Weight ◽  
Ellagic Acid ◽  
Metabolic Diseases ◽  
Diabetes Management ◽  
Protective Effects ◽  
Economic Costs ◽  
Urolithin A ◽  
Causes Of Deaths ◽  
Phase Ii Metabolites ◽  
Urolithin B

Diabetes remains one of the leading causes of deaths and co-morbidities in the world, with tremendous human, social and economic costs. Therefore, despite therapeutics and technological advancements, improved strategies to tackle diabetes management are still needed. One of the suggested strategies is the consumption of (poly)phenols. Positive outcomes of dietary (poly)phenols have been pointed out towards different features in diabetes. This is the case of ellagitannins, which are present in numerous foodstuffs such as pomegranate, berries, and nuts. Ellagitannins have been reported to have a multitude of effects on metabolic diseases. However, these compounds have high molecular weight and do not reach circulation at effective concentrations, being metabolized in smaller compounds. After being metabolized into ellagic acid in the small intestine, the colonic microbiota hydrolyzes and metabolizes ellagic acid into dibenzopyran-6-one derivatives, known as urolithins. These low molecular weight compounds reach circulation in considerable concentrations ranging until micromolar levels, capable of reaching target tissues. Different urolithins are formed throughout the metabolization process, but urolithin A, isourolithin A, and urolithin B, and their phase-II metabolites are the most frequent ones. In recent years, urolithins have been the focus of attention in regard to their effects on a multiplicity of chronic diseases, including cancer and diabetes. In this review, we will discuss the latest advances about the protective effects of urolithins on diabetes.

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

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.

scholarly journals A Comparative Study of Gallic Acid, Ellagic Acid, Urolithin A, and Urolithin B with NF-κB Protein as Anti Type 2 Diabetes Mellitus by In Silico

JSMARTech ◽  
2020 ◽  
Vol 1 (2) ◽  
pp. 31-35
Author(s):  
Maulida Hikmaranti ◽  
◽  
Ajeng M. Astiyani ◽  
Khairul M. Hasanah ◽  
Nuril M. Maghfiroh ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Comparative Study ◽  
Gallic Acid ◽  
Ellagic Acid ◽  
In Silico ◽  
Urolithin A ◽  
Urolithin B

scholarly journals Immunomodulatory Role of Urolithin A on Metabolic Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 192
Author(s):  
Ashley Mulcahy Toney ◽  
Darius Fox ◽  
Virginia Chaidez ◽  
Amanda E. Ramer-Tait ◽  
Soonkyu Chung
Keyword(s):  
Ellagic Acid ◽  
Dietary Intervention ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Alcoholic Fatty Liver ◽  
Urolithin A ◽  
Anti Inflammatory ◽  
The Brain

Urolithin A (UroA) is a gut metabolite produced from ellagic acid-containing foods such as pomegranates, berries, and walnuts. UroA is of growing interest due to its therapeutic potential for various metabolic diseases based on immunomodulatory properties. Recent advances in UroA research suggest that UroA administration attenuates inflammation in various tissues, including the brain, adipose, heart, and liver tissues, leading to the potential delay or prevention of the onset of Alzheimer’s disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. In this review, we focus on recent updates of the anti-inflammatory function of UroA and summarize the potential mechanisms by which UroA may help attenuate the onset of diseases in a tissue-specific manner. Therefore, this review aims to shed new insights into UroA as a potent anti-inflammatory molecule to prevent immunometabolic diseases, either by dietary intervention with ellagic acid-rich food or by UroA administration as a new pharmaceutical drug.

scholarly journals Urolithin A and B Alter Cellular Metabolism and Induce Metabolites Associated with Apoptosis in Leukemic Cells

2021 ◽  
Vol 22 (11) ◽  
pp. 5465
Author(s):  
Abdulaziz Musa Alzahrani ◽  
Mohammed Razeeth Shait Mohammed ◽  
Raed Ahmed Alghamdi ◽  
Abrar Ahmad ◽  
Mazin A. Zamzami ◽  
...  
Keyword(s):  
Cell Lines ◽  
Ellagic Acid ◽  
Cell Metabolism ◽  
Leukemic Cell ◽  
Glutamine Metabolism ◽  
Leukemic Cells ◽  
Leukemic Cell Lines ◽  
Urolithin A ◽  
One Carbon Metabolism ◽  
Urolithin B

Leukemia is persistently a significant cause of illness and mortality worldwide. Urolithins, metabolites of ellagic acid and ellagitannins produced by gut microbiota, showed better bioactive compounds liable for the health benefits exerted by ellagic acid and ellagitannins containing pomegranate and walnuts. Here, we assessed the potential antileukemic activities of both urolithin A and urolithin B. Results showed that both urolithin A and B significantly inhibited the proliferation of leukemic cell lines Jurkat and K562, among which urolithin A showed the more prominent antiproliferative capability. Further, urolithin treatment alters leukemic cell metabolism, as evidenced by increased metabolic rate and notable changes in glutamine metabolism, one-carbon metabolism, and lipid metabolism. Next, we evidenced that both urolithins equally promoted apoptosis in leukemic cell lines. Based on these observations, we concluded that both urolithin A and B alter leukemic cell metabolome, resulting in a halt of proliferation, followed by apoptosis. The data can be used for designing new combinational therapies to eradicate leukemic cells.

scholarly journals Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism

2020 ◽  
Vol 6 (1) ◽  
pp. eaax6208 ◽  
Author(s):  
Su-Ling Zeng ◽  
Shang-Zhen Li ◽  
Ping-Ting Xiao ◽  
Yuan-Yuan Cai ◽  
Chu Chu ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Amino Acid ◽  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Amplicon Sequencing ◽  
Therapeutic Interventions ◽  
Protective Effects ◽  
Fecal Microbiome ◽  
Metabolomic Profiling ◽  
Branched Chain

Metabolic syndrome (MetS) is intricately linked to dysregulation of gut microbiota and host metabolomes. Here, we first find that a purified citrus polymethoxyflavone-rich extract (PMFE) potently ameliorates high-fat diet (HFD)–induced MetS, alleviates gut dysbiosis, and regulates branched-chain amino acid (BCAA) metabolism using 16S rDNA amplicon sequencing and metabolomic profiling. The metabolic protective effects of PMFE are gut microbiota dependent, as demonstrated by antibiotic treatment and fecal microbiome transplantation (FMT). The modulation of gut microbiota altered BCAA levels in the host serum and feces, which were significantly associated with metabolic features and actively responsive to therapeutic interventions with PMFE. Notably, PMFE greatly enriched the commensal bacterium Bacteroides ovatus, and gavage with B. ovatus reduced BCAA concentrations and alleviated MetS in HFD mice. PMFE may be used as a prebiotic agent to attenuate MetS, and target-specific microbial species may have unique therapeutic promise for metabolic diseases.

scholarly journals Ellagic Acid and Its Microbial Metabolite Urolithin a Alleviate Diet-induced Insulin Resistance in Mice (OR24-03-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jieping Yang ◽  
Yuanqian Guo ◽  
Susanne Henning ◽  
Brenda Chan ◽  
Jianfeng Long ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Ellagic Acid ◽  
Microbial Metabolite ◽  
Urolithin A
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