Epigallocatechin gallate

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"EGCG" redirects here. For the software, see Extended GCG.
Epigallocatechin gallate
Structural formula of epigallocatechin gallate
Space-filling model of the epigallocatechin gallate molecule
Names
IUPAC name
[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)chroman-3-yl] 3,4,5-trihydroxybenzoate
Preferred IUPAC name
(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3-yl 3,4,5-trihydroxybenzoate
Other names
(-)-Epigallocatechin gallate
Identifiers
989-51-5 N
ChEBI CHEBI:4806 YesY
ChEMBL ChEMBL297453 YesY
ChemSpider 58575 YesY
7002
Jmol-3D images Image
MeSH Epigallocatechin+gallate
PubChem 65064
Properties
C22H18O11
Molar mass 458.372 g/mol
Appearance
soluble (33.3-100 g/L)[vague][1]
Solubility soluble in ethanol, DMSO, dimethyl formamide[1] at about 20 g/l[2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
 N verify (what isYesY/N?)
Infobox references

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[edit]

Tea[edit]

It is found in high content in the dried leaves of white tea (4245 mg per 100 g), green tea (7380 mg per 100 g) and, in smaller quantities, black tea.[3] During black tea production, the catechins are mostly converted to theaflavins and thearubigins.[4] via polyphenol oxidases.[which?]

Other[edit]

Trace amounts are found in apple skin, plums, onions, hazelnuts, pecans and carob powder (at 109 mg per 100 g).[3]

Bioavailability[edit]

When taken orally, EGCG has poor bioavailability at 800 mg of daily intake equivalent to 8-16 cups of tea which caused only mild adverse effects, such as nausea or heartburn.[5]

Research on potential therapeutic uses[edit]

EGCG has been the subject of a number of basic research studies investigating its potential use as a therapeutic for a broad range of disorders.[6] As of January 2015, however, these effects remain unsubstantiated in humans and there are no approved health claims for EGCG in the United States or Europe. The US Food and Drug Administration has issued warning letters against marketers of products claiming that EGCG provides anti-disease effects or overall health benefits.[7]

HIV[edit]

A large amount of research has been conducted investigating the benefit of EGCG from green tea in the treatment of HIV infection, where EGCG has been shown to reduce plaques related to AIDS-related dementia in the laboratory, as well as block gp120.[8][9][10] However, these effects have yet to be confirmed in live human trials, and it does not imply that green tea will cure or block HIV infection. The concentrations of EGCG used in the studies could not be reached by drinking green tea.

Cancer[edit]

There is evidence from rodent and in vitro studies that EGCG may be useful in preventing or treating various gastrointestinal,[11] prostate,[12] and other cancers. However, the dose needed for effectiveness is high, (far higher than is obtainable through drinking tea) and so companies and academic groups have focused on developing novel analogs or combinations to improve the potential for EGCG to be useful in treating or preventing cancer.[13][14]

In vitro research[edit]

In preliminary laboratory research, EGCG is an inhibitor of various enzymes, such as histone acetyltransferase,[15] DNA methyltransferase[16] or tyrosinase.[17]

Stability[edit]

In a high temperature environment[quantify], an epimerization change is more likely to occur[further explanation needed]; however as exposure to boiling water for 30 straight minutes leads to only a 12.4% reduction in the total amount of EGCG, the amount lost in a brief exposure is insignificant. In fact, even when special conditions were used to create temperatures well above that of boiling water, the amount lost increased only slightly.[18]

Drug interactions[edit]

A study using mouse models at the University of Southern California showed that EGCG binds with the anti-cancer drug Velcade, significantly reducing its bioavailability and thereby rendering it therapeutically useless.[19] Schönthal, who headed the study, suggests that consumption of green tea and GTE products be strongly contraindicated for patients undergoing treatment for multiple myeloma and mantle cell lymphoma.[19] EGCG may reduce the bioavailability of the drug sunitinib when they are taken together.[20] EGCG was also found to induce apoptosis in endometrial carcinoma cell line (Ishikawa cells and human primary endometrial carcinoma cells) via ROS generation and p-38 activation.2012 Manohar et al., J Nutr Biochem. 2012 Sep 5 [Epub ahead of print]

Toxicities[edit]

EGCG may have carcinogenic potential. EGCG was, among other tea polyphenols, found to be a strong topoisomerase inhibitor, similar to some chemotherapeutic anticancer drugs, for example, etoposide and doxorubicin.[21][22][23][24][25] This property might be responsible for observed anticarcinogenic effects; however, there is also a carcinogenic potential. High intake of polyphenolic compounds during pregnancy is suspected to increase risk of neonatal leukemia. Bioflavonoid supplements should not be used by pregnant women.[26][27][28] Maternal consumption of tea or coffee during pregnancy may elevate the risk of childhood malignant central nervous system (CNS) tumours through unknown mechanisms.[29]

A study in mice found that a high dose of EGCG raises ALT levels considerably.[30]

Spectral data[edit]

UV spectrum
UV-Vis
Retention time 34.5 min (C18 RP, Acetonitrile 80%)
Lambda-max 274 and 240 nm (see picture)
Extinction coefficient
IR
Major absorption bands cm−1
NMR
Proton NMR


(500 MHz, CD3OD):
d : doublet, dd : doublet of doublets,
m : multiplet, s : singlet

δ :
Carbon-13 NMR
Other NMR data
MS
Masses of
main fragments
ESI-MS [M+H]+ m/z : 459

See also[edit]

References[edit]

  1. ^ a b http://chemicalland21.com/lifescience/foco/%28-%29-EPIGALLOCATECHIN%20GALLATE.htm
  2. ^ http://www.caymanchem.com/pdfs/70935.pdf
  3. ^ a b "USDA Database for the Flavonoid Content of Selected Foods, Release 3" (PDF). US Department of Agriculture. 2011. Retrieved 18 May 2015. 
  4. ^ Lorenz M, Urban J (2009). "Green and Black Tea are Equally Potent Stimuli of NO Production and Vasodilation: New Insights into Tea Ingredients Involved". Basic Research in Cardiology 104 (1): 100–110. doi:10.1007/s00395-008-0759-3. PMID 19101751. 
  5. ^ Chow HH, Cai Y, Hakim IA, Crowell JA, Shahi F, Brooks CA, Dorr RT, Hara Y, Alberts DS (2003). "Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals". Clin Cancer Res 9 (9): 3312–9. PMID 12960117. 
  6. ^ Fürst R, Zündorf I Plant-derived anti-inflammatory compounds: hopes and disappointments regarding the translation of preclinical knowledge into clinical progress. Mediators Inflamm. 2014;2014:146832. doi: 10.1155/2014/146832. PMID 24987194 PMC 4060065
  7. ^ "Inspections, Compliance, Enforcement, and Criminal Investigations: Warning Letter to Fleminger Inc". Food and Drug Administration. 22 February 2010. Retrieved 6 January 2015. 
  8. ^ Williamson MP, McCormick TG, Nance CL, Shearer WT (December 2006). "Epigallocatechin gallate, the main polyphenol in green tea, binds to the T-cell receptor, CD4: Potential for HIV-1 therapy". The Journal of Allergy and Clinical Immunology 118 (6): 1369–74. doi:10.1016/j.jaci.2006.08.016. PMID 17157668. 
  9. ^ Hamza A, Zhan CG (February 2006). "How can (-)-epigallocatechin gallate from green tea prevent HIV-1 infection? Mechanistic insights from computational modeling and the implication for rational design of anti-HIV-1 entry inhibitors". The Journal of Physical Chemistry. B 110 (6): 2910–7. doi:10.1021/jp0550762. PMID 16471901. 
  10. ^ Yamaguchi K, Honda M, Ikigai H, Hara Y, Shimamura T (January 2002). "Inhibitory effects of (-)-epigallocatechin gallate on the life cycle of human immunodeficiency virus type 1 (HIV-1)". Antiviral Research 53 (1): 19–34. doi:10.1016/S0166-3542(01)00189-9. PMID 11684313. 
  11. ^ "Molecular mechanisms of chemopreventive phytochemicals against gastroenterological cancer development.". World J Gastroenterol 19 (7): 984–93. Feb 2013. doi:10.3748/wjg.v19.i7.984. PMC 3582010. PMID 23467658. 
  12. ^ "New insights into the mechanisms of green tea catechins in the chemoprevention of prostate cancer.". Nutr Cancer 64 (1): 4–22. 2012. doi:10.1080/01635581.2012.630158. PMC 3665011. PMID 22098273. 
  13. ^ "Novel epigallocatechin gallate analogs as potential anticancer agents: a patent review (2009 - present).". Expert Opin Ther Pat 23 (2): 189–202. Feb 2013. doi:10.1517/13543776.2013.743993. PMC 3840390. PMID 23230990. 
  14. ^ "EGCG, green tea polyphenols and their synthetic analogs and prodrugs for human cancer prevention and treatment.". Adv Clin Chem 53: 155–77. 2011. doi:10.1016/b978-0-12-385855-9.00007-2. PMC 3304302. PMID 21404918. 
  15. ^ Choi, K-C; Jung, MG; Lee, Y-H; Yoon, JC; Kwon, SH; Kang, H-B et al. (2009). "Epigallocatechin-3-Gallate, a Histone Acetyltransferase Inhibitor, Inhibits EBV-Induced B Lymphocyte Transformation via Suppression of RelA Acetylation". Cancer Res 69 (2): 583–92. doi:10.1158/0008-5472.can-08-2442. 
  16. ^ Lee, WJ; Shim, J-Y; Zhu, BT. "Mechanisms for the Inhibition of DNA Methyltransferases by Tea Catechins and Bioflavonoids". Mol Pharmacol 68 (4): 1018–30. doi:10.1124/mol.104.008367. 
  17. ^ Sato, Kazuomi; Toriyama, Masaru. "Depigmenting Effect https://web.archive.org/web/20150523193457/http://www.mdpi.com/1420-3049/14/11/4425/pdfof Catechins". mdpi.com. Molecules — Open Access Organic Chemistry Journal. doi:10.3390/molecules14114425. Archived from the original on 23 May 2015. Retrieved 23 May 2015. 
  18. ^ Wang R, Zhou W, Jiang X (April 2008). "Reaction kinetics of degradation and epimerization of epigallocatechin gallate (EGCG) in aqueous system over a wide temperature range". Journal of Agricultural and Food Chemistry 56 (8): 2694–701. doi:10.1021/jf0730338. PMID 18361498. 
  19. ^ a b Neith, Katie. "Green tea blocks benefits of cancer drug, study finds". Retrieved 2009-02-04. 
  20. ^ Ge, J; Tan, BX; Chen, Y; Yang, L; Peng, XC; Li, HZ; Lin, HJ; Zhao, Y; Wei, M; Cheng, K; Li, LH; Dong, H; Gao, F; He, JP; Wu, Y; Qiu, M; Zhao, YL; Su, JM; Hou, JM; Liu, JY (2011). "Interaction of green tea polyphenol epigallocatechin-3-gallate with sunitinib: potential risk of diminished sunitinib bioavailability". J Mol Med (Berl) 89 (6): 595–602. doi:10.1007/s00109-011-0737-3. 
  21. ^ Neukam, K.; Pastor, N.; Cortés, F. (Jun 2008). "Tea flavanols inhibit cell growth and DNA topoisomerase II activity and induce endoreduplication in cultured Chinese hamster cells". Mutat Res 654 (1): 8–12. doi:10.1016/j.mrgentox.2008.03.013. PMID 18541453. 
  22. ^ Berger, SJ.; Gupta, S.; Belfi, CA.; Gosky, DM.; Mukhtar, H. (Oct 2001). "Green tea constituent (-)-epigallocatechin-3-gallate inhibits topoisomerase I activity in human colon carcinoma cells". Biochem Biophys Res Commun 288 (1): 101–5. doi:10.1006/bbrc.2001.5736. PMID 11594758. 
  23. ^ Suzuki, K.; Yahara, S.; Hashimoto, F.; Uyeda, M. (Sep 2001). "Inhibitory activities of (-)-epigallocatechin-3-O-gallate against topoisomerases I and II". Biol Pharm Bull 24 (9): 1088–90. doi:10.1248/bpb.24.1088. PMID 11558576. 
  24. ^ Bandele, OJ.; Osheroff, N. (Apr 2008). "(-)-Epigallocatechin gallate, a major constituent of green tea, poisons human type II topoisomerases". Chem Res Toxicol 21 (4): 936–43. doi:10.1021/tx700434v. PMC 2893035. PMID 18293940. 
  25. ^ Bandele, OJ.; Osheroff, N. (May 2007). "Bioflavonoids as poisons of human topoisomerase II alpha and II beta". Biochemistry 46 (20): 6097–108. doi:10.1021/bi7000664. PMC 2893030. PMID 17458941. 
  26. ^ Paolini, M.; Sapone, A.; Valgimigli, L. (Jun 2003). "Avoidance of bioflavonoid supplements during pregnancy: a pathway to infant leukemia?". Mutat Res 527 (1–2): 99–101. doi:10.1016/S0027-5107(03)00057-5. PMID 12787918. 
  27. ^ Strick, R.; Strissel, PL.; Borgers, S.; Smith, SL.; Rowley, JD. (Apr 2000). "Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia". Proc Natl Acad Sci U S A 97 (9): 4790–5. doi:10.1073/pnas.070061297. PMC 18311. PMID 10758153. 
  28. ^ Ross, JA. (Apr 2000). "Dietary flavonoids and the MLL gene: A pathway to infant leukemia?". Proc Natl Acad Sci U S A 97 (9): 4411–3. doi:10.1073/pnas.97.9.4411. PMC 34309. PMID 10781030. 
  29. ^ Plichart, M.; Menegaux, F.; Lacour, B.; Hartmann, O.; Frappaz, D.; Doz, F.; Bertozzi, AI.; Defaschelles, AS. et al. (Aug 2008). "Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy and childhood malignant central nervous system tumours: the ESCALE study (SFCE)". Eur J Cancer Prev 17 (4): 376–83. doi:10.1097/CEJ.0b013e3282f75e6f. PMC 2746823. PMID 18562965. 
  30. ^ Lambert, K.; Kennett, M.; Sang, S.; Reuhl, K.; Yang, C. (Jan 2010). "Hepatotoxicity of High Oral Dose (-)-Epigallocatechin-3-Gallate in Mice". Food Chem Toxicology 48 (1): 409–416. doi:10.1016/j.fct.2009.10.030.