Epicatechin gallate

Not to be confused with EGCG.

Epicatechin gallate (ECG, (−)-epicatechin-3-gallate) is a flavan-3-ol, a type of flavonoid, primarily found in green tea (Camellia sinensis), with smaller amounts in cocoa, grapes, and other plants. It is also reported in buckwheat and in grape.^[1][2]

Epicatechin gallate

Chemical structure of epicatechin gallate
Chemical structure of epicatechin gallate
Names
IUPAC name (2R,3R)-3′,4′,5,7-Tetrahydroxyflavan-3-yl 3,4,5-trihydroxybenzoate
Systematic IUPAC name (2R,3R)-2-(3,4-Dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-1-benzopyran-3-yl 3,4,5-trihydroxybenzoate
Other names ECG Epicatechin 3-gallate (−)-Epicatechin-3-O-gallate
Identifiers
CAS Number	1257-08-5 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:70255 N
ChEMBL	ChEMBL36327 N
ChemSpider	97034 N
ECHA InfoCard	100.116.252
KEGG	C22594
PubChem CID	107905
UNII	92587OVD8Z Y
CompTox Dashboard (EPA)	DTXSID70925231
InChI InChI=1S/C22H18O10/c23-11-6-14(25)12-8-19(32-22(30)10-4-16(27)20(29)17(28)5-10)21(31-18(12)7-11)9-1-2-13(24)15(26)3-9/h1-7,19,21,23-29H,8H2/t19-,21-/m1/s1 N Key: LSHVYAFMTMFKBA-TZIWHRDSSA-N N InChI=1/C22H18O10/c23-11-6-14(25)12-8-19(32-22(30)10-4-16(27)20(29)17(28)5-10)21(31-18(12)7-11)9-1-2-13(24)15(26)3-9/h1-7,19,21,23-29H,8H2/t19-,21-/m1/s1 Key: LSHVYAFMTMFKBA-TZIWHRDSBY
SMILES O=C(O[C@@H]2Cc3c(O[C@@H]2c1ccc(O)c(O)c1)cc(O)cc3O)c4cc(O)c(O)c(O)c4
Properties
Chemical formula	C22H18O10
Molar mass	442.37 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

As a polyphenolic catechin, ECG is formed by the esterification of epicatechin with gallic acid, contributing to antioxidant, antimicrobial, and potential anticancer properties. ECG is studied for its ability to reverse methicillin resistance in Staphylococcus aureus and inhibit inflammatory pathways, but its clinical use is limited by poor bioavailability and thermal instability in boiling water.^[3] Recent research highlights its potential in modulating SARS-CoV-2-related inflammation and bacterial virulence factors.^[4][5][6]

Epicatechin, as well as many other flavonoids, has been found to act as a nonselective antagonist of the opioid receptors, albeit with somewhat low affinity.^[7]

Chemical structure and properties

ECG is a flavonoid with a molecular formula of C22H18O10 and a molecular weight of 442.373 g/mol. Its structure comprises a flavan-3-ol backbone (epicatechin) esterified with gallic acid at the 3-position, featuring two catechol rings and a trihydroxybenzoate ring with multiple hydroxyl groups. These hydroxyls enable antioxidant activity by scavenging free radicals and chelating metal ions.^[3] The galloyl moiety enhances ECG’s radical scavenging compared to epicatechin, with a DPPH assay showing higher antioxidant activity due to the additional hydroxyl groups.^[8] ECG is soluble in water, ethanol, and DMSO but degrades significantly in boiling water, limiting its stability in tea preparation.

Pharmacological and biological activities

ECG exhibits antioxidant, antimicrobial, anti-inflammatory, and potential anticancer effects. Its antioxidant activity reduces lipid peroxidation and reactive oxygen species (ROS), potentially lowering cardiovascular risk.^[9] ECG inhibits the NorA efflux pump in Staphylococcus aureus, reducing methicillin resistance more effectively than EGCG at low concentrations (IC50 ~50 μM). It also disrupts staphylococcal virulence by reducing coagulase and α-toxin secretion, likely via membrane intercalation.^[10] In cancer models, ECG induces apoptosis in breast cancer cells via caspase-3 activation and inhibits DNA methyltransferase, reactivating silenced genes. A 2022 study showed ECG binds inflammatory mediators (e.g., IL-6, TNF-α, NF-κB) in SARS-CoV-2 infection with docking affinities of −7.3 to −8.3 kcal/mol, suggesting anti-inflammatory potential.^[4]

Metabolism and bioavailability

ECG is absorbed in the intestine, where gut microbiota metabolize it into gallic acid and pyrogallol derivatives. A 2003 study in Wistar rats identified plasma metabolites like 3′-O-methyl-ECG and 4′-O-methyl-ECG, with conjugated pyrogallol as the primary urinary metabolite.^[11] Efflux transporters (e.g., P-gp, MRPs) limit ECG’s bioavailability compared to epicatechin, with the galloyl group reducing absorption efficiency.^[11] Microbial hydrolysis by bacteria like Bifidobacterium longum degrades ECG into gallic acid, further reducing systemic levels.^[12] Encapsulation in zein-chitosan nanoparticles improves stability, enhancing antioxidant activity by up to 95%.^[11]

Natural sources

ECG is a major catechin in green tea, constituting 5–6% of total catechins, alongside epigallocatechin gallate (EGCG), epigallocatechin (EGC), and epicatechin (EC). Its content is lower in black tea due to oxidation into theaflavins during fermentation.

ECG is also present in cocoa (1.2–2.8 mg/g dry weight), grapes, apples, blackberries, cherries, pears, raspberries, red wine, and edible flowers like rose petals and daylilies.^{[citation needed]} In palms, ECG is found in seeds and husk fibers, contributing to antioxidant activity.^{[citation needed]} Green tea’s high ECG content results from minimal processing, preserving polyphenols during steam-drying.^[9]