Epigallocatechin gallate

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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
Jmol-3D images Image
MeSH Epigallocatechin+gallate
PubChem 65064
Properties
C22H18O11
Molar mass 458.37 g·mol−1
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 noted otherwise, data is 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 supplements.

Food sources[edit]

Tea[edit]

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] via polyphenol oxidases.[which?]

Other[edit]

It is also found in various vegetables[which?], nuts, as well as carob powder at 109 mg per 100g.[4]


Pharmacology[edit]

EGCG is an inhibitor of the enzymes:

and antagonises the Epidermal growth factor receptor 1 and Epidermal growth factor receptor 2.[11]

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.[12]

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.[13] 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.[14]

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.[15][16][17] 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,[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]

Spinal muscular atrophy[edit]

Sakla and Lorson found that EGCG increases the number of SMN transcripts in spinal muscular atrophy cells, most probably through modulation of alternative splicing.[22]

Neurodegeneration[edit]

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.[23] 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[24]

CB1 receptor activity[edit]

EGCG has a binding affinity of Ki=33.6μM towards the first cannabinoid receptor, CB1.[25]

Cerebrovascular insult[edit]

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.[26]

Drug interactions[edit]

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.[27] 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.[27] EGCG may reduce the bioavailability of the drug sunitinib when they are taken together.[28] 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[edit]

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.[29]

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.[30][31][32][33][34] 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.[35][36][37] Maternal consumption of tea or coffee during pregnancy may elevate the risk of childhood malignant central nervous system (CNS) tumours through unknown mechanisms.[38]

A study in mice found that a high dose of EGCG raises ALT levels considerably.[39]

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. ^ 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. ^ 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. 
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  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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
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  23. ^ 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. 
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