:Epigallocatechin gallate

{{Short description|Catechin (polyphenol) in tea}}

{{redirect|EGCG|the software|Extended GCG}}

{{chembox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 470454774

| ImageFile=Epigallocatechin gallate structure.svg

| ImageSize=250

| ImageAlt=Structural formula of epigallocatechin gallate

| ImageFile2 = Epigallocatechin gallate 3D spacefill.png

| ImageSize2=240

| ImageAlt2=Space-filling model of the epigallocatechin gallate molecule

| IUPACName=(2R,3R)-3′,4′,5,5′,7-Pentahydroxyflavan-3-yl 3,4,5-trihydroxybenzoate

| SystematicName=(2R,3R)-5,7-Dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3-yl 3,4,5-trihydroxybenzoate

| OtherNames=(-)-Epigallocatechin gallate
(2R,3R)-3′,4′,5,5′,7-pentahydroxyflavan-3-yl gallate

|Section1={{Chembox Identifiers

| IUPHAR_ligand = 7002

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 58575

| InChI = 1/C22H18O11/c23-10-5-12(24)11-7-18(33-22(31)9-3-15(27)20(30)16(28)4-9)21(32-17(11)6-10)8-1-13(25)19(29)14(26)2-8/h1-6,18,21,23-30H,7H2/t18-,21-/m1/s1

| InChIKey = WMBWREPUVVBILR-WIYYLYMNBM

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 297453

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C22H18O11/c23-10-5-12(24)11-7-18(33-22(31)9-3-15(27)20(30)16(28)4-9)21(32-17(11)6-10)8-1-13(25)19(29)14(26)2-8/h1-6,18,21,23-30H,7H2/t18-,21-/m1/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = WMBWREPUVVBILR-WIYYLYMNSA-N

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo=989-51-5

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = BQM438CTEL

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = C09731

| PubChem=65064

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 4806

| SMILES = O=C(O[C@@H]2Cc3c(O[C@@H]2c1cc(O)c(O)c(O)c1)cc(O)cc3O)c4cc(O)c(O)c(O)c4

| MeSHName=Epigallocatechin+gallate

}}

|Section2={{Chembox Properties

| C=22 | H=18 | O=11

| MolarMass = 458.372 g/mol

| Appearance=

| Density=

| MeltingPt=

| BoilingPt=

| Solubility=soluble (5 g/L){{vague|date=May 2013}}{{cite web |title=(−)-Epigallocatechin gallate |website=Chemicalland21.com |url=https://www.sigmaaldrich.com/catalog/product/sigma/e4143?lang=en®ion=GB}}

| SolubleOther=soluble in ethanol, DMSO, dimethyl formamide at about 20 g/L

}}

|Section3={{Chembox Hazards

| MainHazards=

| FlashPt=

| AutoignitionPt =

}}

}}

Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is the ester of epigallocatechin and gallic acid, and is a type of catechin.

EGCG – the most abundant catechin in tea – is a polyphenol under basic research for its potential to affect human health and disease. EGCG is used in many dietary supplements.

Food sources

=Tea=

It is found in high content in the dried leaves of green tea (7380 mg per 100 g), white tea (4245 mg per 100 g), and in smaller quantities, black tea (936 mg per 100 g).{{cite report|url=http://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/Flav/Flav_R03.pdf|title=USDA Database for the Flavonoid Content of Selected Foods, Release 3|last1=Bhagwat|first1=Seema|last2=Haytowitz|first2=David B.|date=September 2011|publisher=Agricultural Research Service, U.S. Department of Agriculture|pages=2, 98–103|last3=Holden|first3=Joanne M.|access-date=18 May 2015}} During black tea production, the catechins are mostly converted to theaflavins and thearubigins via polyphenol oxidases.{{which|date=May 2015}}{{cite journal |first1=Mario |last1=Lorenz |first2=Janka |last2=Urban |first3=Ulrich |last3=Engelhardt |first4=Gert |last4=Baumann |first5=Karl |last5=Stangl |first6=Verena |last6=Stangl |date=January 2009 |pmid=19101751 |title=Green and Black Tea are Equally Potent Stimuli of NO Production and Vasodilation: New Insights into Tea Ingredients Involved |journal=Basic Research in Cardiology |volume=104 |issue=1 |pages=100–110 |doi=10.1007/s00395-008-0759-3 |s2cid=20844066 }}

=Other=

Trace amounts are found in apple skin, plums, onions, hazelnuts, pecans, and carob powder (at 109 mg per 100 g).

Bioavailability

When taken orally, EGCG has poor absorption even at daily intake equivalent to 8 to 16 cups of green tea, an amount causing adverse effects such as nausea or heartburn.{{cite journal |journal=Clinical Cancer Research |date=15 August 2003 |volume=9 |issue=9 |pages=3312–3319 |title=Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals |first1=H.-H. Sherry |last1=Chow |first2=Yan |last2=Cai |first3=Iman A. |last3=Hakim |first4=James A. |last4=Crowell |first5=Farah |last5=Shahi |first6=Chris A. |last6=Brooks |first7=Robert T. |last7=Dorr |first8=Yukihiko |last8=Hara |first9=David S. |last9=Alberts |pmid=12960117 |url=http://clincancerres.aacrjournals.org/content/9/9/3312.long}} After consumption, EGCG blood levels peak within 1.7 hours. The absorbed plasma half-life is around 5 hours, but with majority of unchanged EGCG excreted into urine over 0 to 8 hours.{{cite journal |journal=Cancer Epidemiology, Biomarkers & Prevention |date=October 2002 |volume=11 |issue=10 Pt 1 |pages=1025–1032 |title=Pharmacokinetics of tea catechins after ingestion of green tea and (−)-epigallocatechin 3-gallate by humans: formation of different metabolites and individual variability |first1=Mao-Jung |last1=Lee |first2=Pius |last2=Maliakal |first3=Laishun |last3=Chen |first4=Xiaofeng |last4=Meng |first5=Flordeliza Y. |last5=Bondoc |first6=Saileta |last6=Prabhu |first7=George |last7=Lambert |first8=Sandra |last8=Mohr |first9=Chung S. |last9=Yang |pmid=12376503 |url=http://cebp.aacrjournals.org/content/11/10/1025.long}} Methylated metabolites appear to have longer half-lives and occur at 8 to 25 times the plasma levels of unmetabolized EGCG.{{cite journal|last1=Manach|first1=C|last2=Williamson|first2=G|last3=Morand|first3=C|last4=Scalbert|first4=A|last5=Rémésy|first5=C|title=Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies|journal=The American Journal of Clinical Nutrition|date=January 2005|volume=81|issue=1 Suppl|pages=230S–242S|pmid=15640486|url=http://ajcn.nutrition.org/content/81/1/230S.long|doi=10.1093/ajcn/81.1.230S|doi-access=free}}

Research

Well-studied in basic research, EGCG has various biological effects in laboratory studies.{{cite journal |last1=Fürst |first1=Robert |last2=Zündorf |first2=Ilse |date=May 2014 |title=Plant-derived anti-inflammatory compounds: hopes and disappointments regarding the translation of preclinical knowledge into clinical progress |journal=Mediators of Inflammation |volume=2014 |page=146832 |id=146832 |doi=10.1155/2014/146832 |pmid=24987194 |pmc=4060065 |doi-access=free }}{{cite journal|last1=Granja|first1=Andreia|last2=Frias|first2=Iúri|last3=Neves|first3=Ana Rute|last4=Pinheiro|first4=Marina|last5=Reis|first5=Salette|title=Therapeutic Potential of Epigallocatechin Gallate Nanodelivery Systems|journal=BioMed Research International|volume=2017|year=2017|pages=1–15|issn=2314-6133|doi=10.1155/2017/5813793|pmid=28791306|pmc=5534279|doi-access=free }}{{cite journal|last1=Wu|first1=Dayong|last2=Wang|first2=Junpeng|last3=Pae|first3=Munkyong|last4=Meydani|first4=Simin Nikbin|title=Green tea EGCG, T cells, and T cell-mediated autoimmune diseases|journal=Molecular Aspects of Medicine|volume=33|issue=1|year=2012|pages=107–118|issn=0098-2997|doi=10.1016/j.mam.2011.10.001|pmid=22020144}}{{cite journal|last1=Riegsecker|first1=Sharayah|last2=Wiczynski|first2=Dustin|last3=Kaplan|first3=Mariana J.|last4=Ahmed|first4=Salahuddin|title=Potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation in rheumatoid arthritis|journal=Life Sciences|volume=93|issue=8|year=2013|pages=307–312|pmid=23871988|pmc=3768132|doi=10.1016/j.lfs.2013.07.006}}

A 2011 analysis by the European Food Safety Authority found that a cause and effect relationship could not be shown for a link between tea catechins and the maintenance of normal blood LDL-cholesterol concentration.{{cite journal |author=EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies) |journal=EFSA Journal |volume=9 |issue=4 |year=2011 |title=Scientific Opinion on the substantiation of health claims related to Camellia sinensis (L.) Kuntze (tea), including catechins in green tea, and improvement of endothelium-dependent vasodilation (ID 1106, 1310), maintenance of normal blood pressure |doi=10.2903/j.efsa.2011.2055 |page=2055|doi-access=free }} A 2016 review found that high daily doses (107 to 856 mg/day) taken by human subjects over four to 14 weeks produced a small reduction of LDL cholesterol.{{cite journal|last1=Momose Y|display-authors=etal|title=Systematic review of green tea epigallocatechin gallate in reducing low-density lipoprotein cholesterol levels of humans.|journal=International Journal of Food Sciences and Nutrition|volume=67|issue=6|year=2016|pages=606–613|pmid=27324590|doi=10.1080/09637486.2016.1196655|s2cid=39704366}}

Potential toxicity

A 2018 review showed that excessive intake of EGCG may cause liver toxicity.{{cite journal|pmid=29580974|year=2018|last1=Hu|first1=J|title=The safety of green tea and green tea extracts consumption in adults – Results of a systematic review|journal=Regulatory Toxicology and Pharmacology|volume=95|pages=412–433|last2=Webster|first2=D|last3=Cao|first3=J|last4=Shao|first4=A|doi=10.1016/j.yrtph.2018.03.019|doi-access=free}} In 2018, the European Food Safety Authority stated that daily intake of 800 mg or more could increase risk of liver damage.{{cite journal|title=Scientific opinion on the safety of green tea catechins|journal=EFSA Journal|volume=16|issue=4|doi=10.2903/j.efsa.2018.5239|date=18 April 2018|display-authors=3|last1=Younes|first1=Maged|last2=Aggett|first2=Peter|last3=Aguilar|first3=Fernando|last4=Crebelli|first4=Riccardo|last5=Dusemund|first5=Birgit|last6=Filipič|first6=Metka|last7=Frutos|first7=Maria Jose|last8=Galtier|first8=Pierre|last9=Gott|first9=David|last10=Gundert‐Remy|first10=Ursula|last11=Lambré|first11=Claude|last12=Leblanc|first12=Jean‐Charles|last13=Lillegaard|first13=Inger Therese|last14=Moldeus|first14=Peter|last15=Mortensen|first15=Alicja|last16=Oskarsson|first16=Agneta|last17=Stankovic|first17=Ivan|last18=Waalkens‐Berendsen|first18=Ine|last19=Woutersen|first19=Rudolf Antonius|last20=Andrade|first20=Raul J.|last21=Fortes|first21=Cristina|last22=Mosesso|first22=Pasquale|last23=Restani|first23=Patrizia|last24=Arcella|first24=Davide|last25=Pizzo|first25=Fabiola|last26=Smeraldi|first26=Camilla|last27=Wright|first27=Matthew|pages=e05239|pmid=32625874|pmc=7009618|doi-access=free}}

Taken as a capsule or tablet 338 mg per day of EGCG is considered safe, whereas 704 mg per day is safe if consumed as a tea beverage. 100 mL of green tea contains about 70.2 mg of EGCG (about 165 mg per cup).

Regulation

Over 2008 to 2017, the US Food and Drug Administration issued several warning letters to manufacturers of dietary supplements containing EGCG for violations of the Federal Food, Drug, and Cosmetic Act. Most of these letters informed the companies that their promotional materials promoted EGCG-based dietary supplements in the treatment or prevention of diseases or conditions that cause them to be classified as drugs under the United States code,{{cite web |url=http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2008/ucm200918.htm |archive-url=https://wayback.archive-it.org/7993/20161023103651/http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2008/ucm200918.htm |url-status=dead |archive-date=23 October 2016 |publisher=Food and Drug Administration |work=Inspections, Compliance, Enforcement, and Criminal Investigations |title=Sharp Labs Inc: Warning Letter |date=9 July 2008 |access-date=15 September 2015 }}{{cite web |url=http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2010/ucm202823.htm |archive-url=https://wayback.archive-it.org/7993/20161023102337/http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2010/ucm202823.htm |url-status=dead |archive-date=23 October 2016 |publisher=Food and Drug Administration |work=Inspections, Compliance, Enforcement, and Criminal Investigations |title=Fleminger Inc.: Warning Letter |date=22 February 2010 |access-date=6 January 2015 }}{{cite web |url=https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2017/ucm554234.htm |archive-url=https://web.archive.org/web/20170426064311/https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2017/ucm554234.htm |url-status=dead |archive-date=April 26, 2017 |publisher=Food and Drug Administration |work=Inspections, Compliance, Enforcement, and Criminal Investigations |title=LifeVantage Corporation: Warning Letter |date=17 April 2017|access-date=30 September 2017}} while another focused on inadequate quality assurance procedures and labeling violations.{{cite web |url=https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2013/ucm364258.htm |archive-url=https://web.archive.org/web/20140310001443/http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2013/ucm364258.htm |url-status=dead |archive-date=March 10, 2014 |publisher=Food and Drug Administration |work=Inspections, Compliance, Enforcement, and Criminal Investigations |title=N.V.E. Pharmaceuticals, Inc.: Warning Letter |date=22 July 2013 |access-date=30 September 2017}} The warnings were issued because the products had not been established as safe and effective for their marketed uses and were promoted as "new drugs", without approval as required under the Act.

See also

References

{{Reflist|2}}

{{Antioxidants}}

{{HIVpharm}}

{{Flavanols}}

{{Estrogen receptor modulators}}

{{Glutamate metabolism and transport modulators}}

{{Teas}}

Category:11β-Hydroxysteroid dehydrogenase inhibitors

Category:Aromatase inhibitors

Category:Flavanols

Category:Gallate esters