Epigallocatechin gallate

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 
ChEBI CHEBI:4806 Yes
ChEMBL ChEMBL297453 Yes
ChemSpider 58575 Yes
Jmol-3D images Image
MeSH Epigallocatechin+gallate
PubChem 65064
Properties
Molecular formula
 C22H18O11
Molar mass 458.37 g·mol−1
Appearance
soluble (33.3-100 g/L)[1]
Solubility soluble in ethanol, DMSO, dimethyl formamide[1] at about 20 g/l[2]
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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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. It is found mainly in white tea, green tea and, in smaller quantities, black tea; during black tea production, the catechins are mostly converted to theaflavins and thearubigins.[3] It is also found in various vegetables, nuts, as well as carob powder at 109 mg per 100g.[4] In a high temperature environment, an epimerization change is more likely to occur; 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.[5]

EGCG is used in many supplements.

Pharmacology

EGCG is an inhibitor of the enzymes:

and antagonises the Epidermal growth factor receptor 1 and Epidermal growth factor receptor 2.[12]

Research on potential therapeutic uses

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. 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.[13]

HIV

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.[14][15][16] 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, but it may help regulate viral load as long as it is not involved in adverse drug reactions. The concentrations of EGCG used in the studies could not be reached by drinking green tea. More study into EGCG and HIV is currently underway.[17]

Cancer

There is evidence from rodent and in vitro studies that EGCG may be useful in preventing or treating various gastrointestinal,[18] prostate,[19] 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.[20][21]

Chronic fatigue syndrome

Research at Panjab University Chandigarh found that EGCG is effective in various mouse models of chronic fatigue syndrome.[22][23][24]

Sjögren's syndrome

Research at Medical College of Georgia found that EGCG was effective in a mouse model of Sjögren's syndrome.[25]

Endometriosis

Xu et al. found that EGCG reduce lesion size in a mouse model of endometriosis.[26]

Spinal muscular atrophy

Sakla and Lorson found that EGCG increases the number of SMN transcripts in spinal muscular atrophy cells, most probably through modulation of alternative splicing.[27]

Neurodegeneration

EGCG is a natural chelator and has been shown to reduce iron-accumulation in instances of neurodegenerative diseases like dementia, Alzheimer's, and Parkinson's.[28] Parc de Salut Mar and Instituto Hospital del Mar de Investigaciones Médicas in Spain are conducting a clinical trial of EGCG as a potential treatment for intellectual impairment in people with Down Syndrome and Fragile X[29]

CB1 receptor activity

EGCG has a binding affinity of Ki=33.6μM towards the first cannabinoid receptor, CB1.[30]

Periapical lesions

There are in vitro data about theurapeutic potential of EGCG in periapical periodontitis.[31]

Cerebrovascular insult

EGCG improves neurological status of rats that have undergone middle cerebral artery occlusion (a common stroke model). A possible mechanism is inhibition of calpain- mediated TRPC6 proteolysis.[32]

Drug interactions

A study using mouse models at the University of Southern California showed that, in contrast to the myriad benefits commonly associated with green tea and green tea extract (GTE), EGCG binds with the anti-cancer drug Velcade, significantly reducing its bioavailability and thereby rendering it therapeutically useless.[33] 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.[33] EGCG may reduce the bioavailability of the drug sunitinib when they are taken together.[34] 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]

Bioavailability

Bioavailability when taken orally is poor and 800 mg of oral EGCG results in concentrations an order of magnitude lower than what has proven efficacious.[35]

Toxicities

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.[36][37][38][39][40] 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.[41][42][43] Maternal consumption of tea or coffee during pregnancy may elevate the risk of childhood malignant central nervous system (CNS) tumours through unknown mechanisms.[44]

A study in mice found that a high dose of EGCG raises ALT levels considerably.[45]

Spectral data

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

References

  1. ↑ 1.0 1.1 http://chemicalland21.com/lifescience/foco/%28-%29-EPIGALLOCATECHIN%20GALLATE.htm
  2. ↑ http://www.caymanchem.com/pdfs/70935.pdf
  3. ↑ 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.
  4. ↑ http://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/Flav/Flav_R03.pdf
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ Baron, A; Migita, T; Tang, D; Loda, M. "Fatty acid synthase: A metabolic oncogene in prostate cancer?". Journal of Cellular Biochemistry 91 (1): 47–53. doi:10.1002/jcb.10708.
  9. ↑ Li, C; Allen, A; Kwagh, J; Doliba, NM; Qin, W; Najafi, H et al. "Green Tea Polyphenols Modulate Insulin Secretion by Inhibiting Glutamate Dehydrogenase". J Biol Chem 281 (15): 10214–21. doi:10.1074/jbc.m512792200.
  10. ↑ Suzuki, K; Yahara, S; Hashimoto, F; Uyeda, M (2001). "Inhibitory Activities of (-)-Epigallocatechin-3-O-gallate against Topoisomerases I and II". Biological and Pharmaceutical Bulletin 24 (9): 1088–90. doi:10.1248/bpb.24.1088. PMID 11558576.
  11. ↑ Biochem Bertoldi, M; Gonsalvi, M; Voltattorni, CB (Jun 2001). "Green tea polyphenols: novel irreversible inhibitors of dopa decarboxylase". Biophys Res Commun 284 (1): 90–3. doi:10.1006/bbrc.2001.4945.
  12. ↑ Shimizu M, Deguchi A, Lim JTE, Moriwaki H, Kopelovich L, Weinstein IB. (−)-Epigallocatechin Gallate and Polyphenon E Inhibit Growth and Activation of the Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor-2 Signaling Pathways in Human Colon Cancer Cells. Clin Cancer Res [Internet]. 2005 Apr 1 [cited 2013 Aug 28];11(7):2735–46. Available from: http://clincancerres.aacrjournals.org/content/11/7/2735
  13. ↑ "Inspections, Compliance, Enforcement, and Criminal Investigations: Warning Letter to Fleminger Inc". Food and Drug Administration. 22 February 2010. Retrieved 6 January 2015.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ Nance CL, Shearer WT (November 2003). "Is green tea good for HIV-1 infection?". The Journal of Allergy and Clinical Immunology 112 (5): 851–3. doi:10.1016/j.jaci.2003.08.048. PMID 14610469.
  18. ↑ "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.
  19. ↑ "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.
  20. ↑ "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.
  21. ↑ "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.
  22. ↑ Sachdeva, A K; Kuhad, A; Chopra, K (2011). "Epigallocatechin gallate ameliorates behavioral and biochemical deficits in rat model of load-induced chronic fatigue syndrome". Brain Research Bulletin 86 (3–4): 165–72. doi:10.1016/j.brainresbull.2011.06.007. PMID 21821105.
  23. ↑ Sachdeva, A K; Kuhad, A; Tiwari, V; Arora, V; Chopra, K (2010). "Protective effect of epigallocatechin gallate in murine water-immersion stress model of chronic fatigue syndrome". Basic & Clinical Pharmacology & Toxicology 106 (6): 490–96. doi:10.1111/j.1742-7843.2009.00525.x. PMID 20088847.
  24. ↑ Sachdeva, A K; Kuhad, A; Tiwari, V; Chopra, K (2009). "Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence". Behavioural Brain Research 205 (2): 414–20. doi:10.1016/j.bbr.2009.07.020. PMID 1964314.
  25. ↑ Gillespie, K; Kodani, I; Dickinson, DP; Ogbureke, KU; Camba, AM; Wu, M; Looney, S; Chu, TC et al. (2008). "Effects of oral consumption of the green tea polyphenol EGCG in a murine model for human Sjogren's syndrome, an autoimmune disease". Life Sciences 83 (17–18): 581–8. doi:10.1016/j.lfs.2008.08.011. PMC 2701648. PMID 18809413.
  26. ↑ Xu, Hui; Becker, Christian M.; Lui, Wai Ting; Chu, Ching Yan; Davis, Tina N.; Kung, Andrew L.; Birsner, Amy E.; d’Amato, Robert J. et al. (2011). "Green tea epigallocatechin-3-gallate inhibits angiogenesis and suppresses vascular endothelial growth factor C/vascular endothelial growth factor receptor 2 expression and signaling in experimental endometriosis in vivo". Fertility and Sterility 96 (4): 1021–8. doi:10.1016/j.fertnstert.2011.07.008. PMID 21821246.
  27. ↑ Sakla, M. S.; Lorson, C. L. (2007). "Induction of full-length survival motor neuron by polyphenol botanical compounds". Human Genetics 122 (6): 635–643. doi:10.1007/s00439-007-0441-0. PMID 17962980.
  28. ↑ Bai, Yun; Yanyan Wang, Maoquan Li, Xueqing Xu, Min Song, Huansheng Tao, (April 2012). "Green tea epigallocatechin-3-gallate (EGCG) promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis". You have free access to this content Molecular Nutrition & Food Research 56 (8): 1292–1303. doi:10.1002/mnfr.201200035.
  29. ↑ Staff, IMM. Utilización de la epigalocatequina galato (EGCG) para modular Dyrk1A y APP y evaluar su impacto sobre el rendimiento cognitivo en pacientes con síndrome de Down (SD) English translation - Using epigallocatechin gallate (EGCG) to modulate Dyrk1A and APP and evaluate its impact on cognitive performance in patients with Down syndrome (DS) Page Accessed June 7, 2013
  30. ↑ Korte, G.; Dreiseitel, A.; Schreier, P.; Oehme, A.; Locher, S.; Geiger, S.; Heilmann, J.; Sand, P. (2010). "Tea catechins' affinity for human cannabinoid receptors". Phytomedicine : international journal of phytotherapy and phytopharmacology 17 (1): 19–22. doi:10.1016/j.phymed.2009.10.001. PMID 19897346.
  31. ↑ Lee, Y. L.; Hong, C. Y.; Kok, S. H.; Hou, K. L.; Lin, Y. T.; Chen, M. H.; Wang, C. C.; Lin, S. K. (2009). "An Extract of Green Tea, Epigallocatechin-3-Gallate, Reduces Periapical Lesions by Inhibiting Cysteine-rich 61 Expression in Osteoblasts". Journal of Endodontics 35 (2): 206–211. doi:10.1016/j.joen.2008.11.015. PMID 19166774.
  32. ↑ Yao C (Jan 2014). "Neuroprotection by (-)-epigallocatechin-3-gallate in a rat model of stroke is mediated through inhibition of endoplasmic reticulum stress.". J Mol Med Rep 9 (1): 69–76. doi:10.3892/mmr.2013.1778. PMID 24193141.
  33. ↑ 33.0 33.1 Neith, Katie. "Green tea blocks benefits of cancer drug, study finds". Retrieved 2009-02-04.
  34. ↑ 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.
  35. ↑ Template:Cite doi:10.4172/2155-983X.1000117
  36. ↑ 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.
  37. ↑ 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.
  38. ↑ 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.
  39. ↑ 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.
  40. ↑ 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.
  41. ↑ 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.
  42. ↑ 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.
  43. ↑ 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.
  44. ↑ 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.
  45. ↑ 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.