Epicatechin gallate (ECG, (−)-epicatechin-3-gallate) is a

flavan-3-ol Flavan-3-ols (sometimes referred to as flavanols) are a subgroup of flavonoids. They are derivatives of flavans that possess a 2-phenyl-3,4-dihydro-2''H''-chromen-3-ol skeleton. Flavan-3-ols are structurally diverse and include a range of compo ...

, a type of

flavonoid Flavonoids (or bioflavonoids; from the Latin word ''flavus'', meaning yellow, their color in nature) are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans. Chemically, flavonoids ...

, primarily found in

green tea Green tea is a type of tea made from the leaves and buds of the '' Camellia sinensis'' that have not undergone the withering and oxidation process that creates oolong teas and black teas. Green tea originated in China in the late 1st millenn ...

(''Camellia sinensis''), with smaller amounts in cocoa, grapes, and other plants. It is also reported in

buckwheat Buckwheat (''Fagopyrum esculentum'') or common buckwheat is a flowering plant in the knotweed family Polygonaceae cultivated for its grain-like seeds and as a cover crop. Buckwheat originated around the 6th millennium BCE in the region of what ...

and in

grape A grape is a fruit, botanically a berry, of the deciduous woody vines of the flowering plant genus ''Vitis''. Grapes are a non- climacteric type of fruit, generally occurring in clusters. The cultivation of grapes began approximately 8,0 ...

. As a polyphenolic

catechin Catechin is a flavan-3-ol, a type of secondary metabolite providing antioxidant roles in plants. It belongs to the subgroup of polyphenols called flavonoids. The name of the catechin chemical family derives from ''catechu'', which is the tannic ...

, ECG is formed by the esterification of

epicatechin Catechin is a flavan-3-ol, a type of secondary metabolite providing antioxidant roles in plants. It belongs to the subgroup of polyphenols called flavonoids. The name of the catechin chemical family derives from '' catechu'', which is the tann ...

with

gallic acid Gallic acid (also known as 3,4,5-trihydroxybenzoic acid) is a trihydroxybenzoic acid with the formula C6 H2( OH)3CO2H. It is classified as a phenolic acid. It is found in gallnuts, sumac, witch hazel, tea leaves, oak bark, and other plant ...

, contributing to antioxidant, antimicrobial, and potential anticancer properties. ECG is studied for its ability to reverse methicillin resistance in ''

Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...

'' and inhibit inflammatory pathways, but its clinical use is limited by poor bioavailability and thermal instability in boiling water. Recent research highlights its potential in modulating SARS-CoV-2-related inflammation and bacterial virulence factors. Epicatechin, as well as many other flavonoids, has been found to act as a nonselective

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.opioid receptor Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostati ...

s, albeit with somewhat low

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

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. 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. 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. 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. 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.

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. Efflux transporters (e.g., P-gp, MRPs) limit ECG’s bioavailability compared to epicatechin, with the galloyl group reducing absorption efficiency. Microbial hydrolysis by bacteria like ''Bifidobacterium longum'' degrades ECG into gallic acid, further reducing systemic levels. Encapsulation in zein-chitosan nanoparticles improves stability, enhancing antioxidant activity by up to 95%.

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. In palms, ECG is found in seeds and husk fibers, contributing to antioxidant activity. Green tea’s high ECG content results from minimal processing, preserving polyphenols during steam-drying.

Chemical structure and properties

Pharmacological and biological activities

Metabolism and bioavailability

Natural sources

References

See also