Urolithin A

Chemical compound
Urolithin A
Chemical structure of urolithin A
Names
Preferred IUPAC name
3,8-Dihydroxy-6H-dibenzo[b,d]pyran-6-one
Other names
Uro-A
Identifiers
CAS Number
  • 1143-70-0 checkY
3D model (JSmol)
  • Interactive image
ChEMBL
  • ChEMBL1836264
ChemSpider
  • 4589709
DrugBank
  • DB15464
KEGG
  • C22595
PubChem CID
  • 5488186
UNII
  • ILJ8NEF6DT checkY
CompTox Dashboard (EPA)
  • DTXSID40150694 Edit this at Wikidata
InChI
  • InChI=1S/C13H8O4/c14-7-1-3-9-10-4-2-8(15)6-12(10)17-13(16)11(9)5-7/h1-6,14-15H
    Key: RIUPLDUFZCXCHM-UHFFFAOYSA-N
  • InChI=1/C13H8O4/c14-7-1-3-9-10-4-2-8(15)6-12(10)17-13(16)11(9)5-7/h1-6,14-15H
    Key: RIUPLDUFZCXCHM-UHFFFAOYAT
  • Oc1ccc2c3ccc(O)cc3OC(=O)c2c1
Properties
Chemical formula
 C13H8O4
Molar mass 228.203 g·mol−1
Melting point 17
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references
Chemical compound

Urolithin A is a metabolite compound resulting from the transformation of ellagitannins by the gut bacteria.[1] It belongs to the class of organic compounds known as benzo-coumarins or dibenzo-α-pyrones. Its precursors – ellagic acids and ellagitannins – are ubiquitous in nature, including edible plants, such as pomegranates, strawberries, raspberries, walnuts, and others.[2]

Urolithin A is not known to be found in any food source. Its bioavailability mostly depends on individual microbiota composition, as only some bacteria are able to convert ellagitannins into urolithins.[3]

Chemistry

Urolithin A belongs to the class of organic compounds known as benzo-coumarins or dibenzo-α-pyrones. These are polycyclic aromatic compounds containing a 1-benzopyran moiety with a ketone group at the C2 carbon atom (1-benzopyran-2-one).

Biochemistry and metabolism

Pomegranate fruits, walnuts, and raspberries are sources of ellagitannins.[4][5][6] Ellagitannins are hydrolyzed in the gut to release ellagic acid, which is further processed by the gut microflora into urolithins through the loss of one of its two lactones and by successive removal of hydroxyl groups.[7]

While studies have shown that Gordonibacter urolithinfaciens and Gordonibacter pamelaeae play a role in the conversion of ellagic acids and ellagitannins into urolithin A, the microorganisms responsible for the complete transformation into the final urolithins are still unknown.[3] The efficiency of the conversion of ellagitannins into urolithin A significantly varies in humans, and some individuals do not show any conversion.[8]

When synthesized and absorbed in the intestines, urolithin A enters the systemic circulation where it becomes available to tissues throughout the body where it is further subjected to additional chemical transformations (including glucuronidation, methylation, sulfation, or a combination of them) within the enterocytes and hepatocytes.[9] Urolithin A and its derivatives - urolithin A glucuronide and urolithin A sulfate being most abundant - release into the circulation, before being excreted in the urine.[10]

Safety

In vivo studies did not determine any toxicity or specific adverse effects following dietary intake of urolithin A.[11] Safety studies in elderly humans indicated urolithin A was well tolerated.[12] In 2018, the US Food and Drug Administration listed urolithin A as a safe ingredient for food or dietary supplement products having content in the range of 250 mg to one gram per serving.[13]

Dietary sources

Urolithin A is not known to be found in any food but rather forms as the result of transformation of ellagic acids and ellagitannins by the gut microflora in humans.[citation needed] Sources of ellagitannins are: pomegranates, nuts, some berries (raspberries, strawberries, blackberries, cloudberries), tea, muscadine grapes, many tropical fruits, and oak-aged wines (table below).

The conversion of the ellagic acids into urolithin A depends on individual microflora composition and can vary significantly.[8][14]

Dietary source Ellagic Acid[15]
Fruits (mg/100g fresh weight)
Blackberries 150
Black raspberries 90
Boysenberries 70
Cloudberries 315.1
Pomegranate 269.9[16]
Raspberries 270
Rose hip 109.6
Strawberries 77.6
Strawberry jam 24.5
Yellow raspberries 1900
Nuts (mg/g)
Pecans 33
Walnuts 59
Beverages (mg/L)
Pomegranate juice 811.1[16]
Cognac 31-55
Oak-aged red wine 33
Whiskey 1.2
Seeds (mg/g)
Black raspberries 6.7
Red raspberries 8.7
Boysenberries 30
Mango 1.2

See also

References

  1. ^ Garcia-Muñoz C, Vaillant F (2014-12-02). "Metabolic fate of ellagitannins: implications for health, and research perspectives for innovative functional foods". Critical Reviews in Food Science and Nutrition. 54 (12): 1584–98. doi:10.1080/10408398.2011.644643. PMID 24580560. S2CID 5387712.
  2. ^ Cerdá B, Tomás-Barberán FA, Espín JC (January 2005). "Metabolism of antioxidant and chemopreventive ellagitannins from strawberries, raspberries, walnuts, and oak-aged wine in humans: identification of biomarkers and individual variability". Journal of Agricultural and Food Chemistry. 53 (2): 227–35. doi:10.1021/jf049144d. PMID 15656654.
  3. ^ a b Selma MV, Beltrán D, Luna MC, Romo-Vaquero M, García-Villalba R, Mira A, et al. (2017). "Isolation of Human Intestinal Bacteria Capable of Producing the Bioactive Metabolite Isourolithin A from Ellagic Acid". Frontiers in Microbiology. 8: 1521. doi:10.3389/fmicb.2017.01521. PMC 5545574. PMID 28824607.
  4. ^ Johanningsmeier SD, Harris GK (2011-02-28). "Pomegranate as a functional food and nutraceutical source". Annual Review of Food Science and Technology. 2 (1): 181–201. doi:10.1146/annurev-food-030810-153709. PMID 22129380.
  5. ^ Sánchez-González C, Ciudad CJ, Noé V, Izquierdo-Pulido M (November 2017). "Health benefits of walnut polyphenols: An exploration beyond their lipid profile". Critical Reviews in Food Science and Nutrition. 57 (16): 3373–3383. doi:10.1080/10408398.2015.1126218. hdl:2445/99551. PMID 26713565. S2CID 19611576.
  6. ^ Ludwig IA, Mena P, Calani L, Borges G, Pereira-Caro G, Bresciani L, et al. (December 2015). "New insights into the bioavailability of red raspberry anthocyanins and ellagitannins" (PDF). Free Radical Biology & Medicine. 89: 758–69. doi:10.1016/j.freeradbiomed.2015.10.400. PMID 26475039.
  7. ^ Espín JC, Larrosa M, García-Conesa MT, Tomás-Barberán F (2013). "Biological significance of urolithins, the gut microbial ellagic Acid-derived metabolites: the evidence so far". Evidence-Based Complementary and Alternative Medicine. 2013: 270418. doi:10.1155/2013/270418. PMC 3679724. PMID 23781257.
  8. ^ a b Tomás-Barberán FA, González-Sarrías A, García-Villalba R, Núñez-Sánchez MA, Selma MV, García-Conesa MT, Espín JC (January 2017). "Urolithins, the rescue of "old" metabolites to understand a "new" concept: Metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis, and host health status". Molecular Nutrition & Food Research. 61 (1): n/a. doi:10.1002/mnfr.201500901. PMID 27158799.
  9. ^ Tulipani S, Urpi-Sarda M, García-Villalba R, Rabassa M, López-Uriarte P, Bulló M, et al. (September 2012). "Urolithins are the main urinary microbial-derived phenolic metabolites discriminating a moderate consumption of nuts in free-living subjects with diagnosed metabolic syndrome". Journal of Agricultural and Food Chemistry. 60 (36): 8930–40. doi:10.1021/jf301509w. hdl:2445/171748. PMID 22631214. S2CID 43139238.
  10. ^ Truchado P, Larrosa M, García-Conesa MT, Cerdá B, Vidal-Guevara ML, Tomás-Barberán FA, Espín JC (June 2012). "Strawberry processing does not affect the production and urinary excretion of urolithins, ellagic acid metabolites, in humans". Journal of Agricultural and Food Chemistry. 60 (23): 5749–54. doi:10.1021/jf203641r. PMID 22126674.
  11. ^ Heilman J, Andreux P, Tran N, Rinsch C, Blanco-Bose W (October 2017). "Safety assessment of Urolithin A, a metabolite produced by the human gut microbiota upon dietary intake of plant derived ellagitannins and ellagic acid". Food and Chemical Toxicology. 108 (Pt A): 289–297. doi:10.1016/j.fct.2017.07.050. PMID 28757461.
  12. ^ Singh A, Andreux P, Blanco-Bose W, Ryu D, Aebischer P, Auwerx J, Rinsch C (2017-07-01). "Orally administered urolithin A is safe and modulates muscle and mitochondrial biomarkers in elderly". Innovation in Aging. 1 (suppl_1): 1223–1224. doi:10.1093/geroni/igx004.4446. PMC 6183836.
  13. ^ "FDA GRAS notice GRN No. 791: urolithin A". US Food and Drug Administration. 20 December 2018. Retrieved 25 August 2020.
  14. ^ Selma MV, Romo-Vaquero M, García-Villalba R, González-Sarrías A, Tomás-Barberán FA, Espín JC (April 2016). "The human gut microbial ecology associated with overweight and obesity determines ellagic acid metabolism". Food & Function. 7 (4): 1769–74. doi:10.1039/c5fo01100k. PMID 26597167.
  15. ^ Landete JM (2011). "Ellagitannins, ellagic acid and their derived metabolites: A review about source, metabolism, functions and health". Food Research International. 44 (5): 1150–1160. doi:10.1016/j.foodres.2011.04.027.
  16. ^ a b García-Villalba R, Espín JC, Tomás-Barberán FA (January 2016). "Chromatographic and spectroscopic characterization of urolithins for their determination in biological samples after the intake of foods containing ellagitannins and ellagic acid". Journal of Chromatography A. 1428: 162–75. doi:10.1016/j.chroma.2015.08.044. PMID 26341594.

External links