EGCG

Category: flavonoid

Aliases: Epigallocatechin gallate, (-)-Epigallocatechin-3-gallate

Pharmacological Mechanism

Flavan-3-ol gallate ester — the dominant green-tea polyphenol. DNMT1 inhibitor (epigenetic demethylation), 20S proteasome inhibitor (preclinical antineoplastic), COMT inhibitor (extends catecholamine synthesis action — rationale for combined fat-oxidation protocols with caffeine). Potent aqueous-phase antioxidant. Strongest iron-chelator among tea polyphenols (relevant for Fe²⁺ bioavailability reduction).

Half-Life (t½)

PO: 3h

Dosing Guidelines

• PO: Typical 300 mg (Range: 200–500 mg)

Target Organ Systems

• immune-hematologic

Interactions

• Caffeine (synergistic): Caffeine + EGCG — classic fat-oxidation stack (caffeine drives lipolysis; EGCG via COMT inhibition extends catecholamine action).
• Iron (caution): EGCG chelates non-heme iron in the gut. Separate iron supplement by 2 h.
• (+)-Catechin (synergistic): Co-occur in tea; EGCG is the gallate-esterified, more bioactive form.
• (−)-Epicatechin (synergistic): Co-occur in tea; EGCG is the gallated, higher-activity tea flavanol.

Pathways It Modulates

• Alzheimer disease (inhibitor) — Aβ aggregation (preclinical)
• AMPK energy sensor (activator) — AMPK (green tea catechin)
• BDNF / TrkB neurotrophic signaling (activator) — BDNF (anti-inflammatory + CREB)
• Brown adipose thermogenesis (activator) — BAT thermogenesis (modest clinical signal)
• CD4 T-helper differentiation (inhibitor) — Th17 suppression
• Cellular senescence / SASP / senolytics (inhibitor) — SASP / oxidative damage
• cGAS-STING cytosolic DNA sensing → type I IFN (inhibitor) — STING (preclinical)
• Estrogen phase-2 clearance (inhibitor) — COMT (competitive) + phase-2 induction
• Estrogen receptor (ERα / ERβ / GPER) (inhibitor) — ER (chemopreventive)
• Hedgehog / Smoothened signaling (inhibitor) — Hh (chemopreventive)
• Hepcidin / ferroportin iron regulation (inhibitor) — iron chelation + hepcidin modulation
• Kynurenine pathway (inhibitor) — IDO1
• MAPK / ERK (RAS-RAF-MEK-ERK) cascade (inhibitor) — MAPK (chemopreventive)
• Microbiome short-chain fatty acid signaling (activator) — beneficial composition (poorly absorbed → colon)
• Mitophagy (activator) — mitophagy + antioxidant
• Necroptosis (inhibitor) — necroptosis (anti-inflammatory)
• Neuroinflammation (inhibitor) — NF-κB + NLRP3
• Notch signaling (inhibitor) — Notch (chemopreventive)
• Nrf2 / Keap1 antioxidant response (activator) — Nrf2 + COMT inhibition + receptor cross-talk
• p53 / MDM2 DNA-damage response (activator) — p53 + chemoprevention (catechin)
• Parkinson disease (inhibitor) — α-synuclein aggregation (catechin direct binding)
• Pyroptosis (inhibitor) — NLRP3 / NF-κB priming
• TLR (Toll-like receptor) innate signaling (inhibitor) — TLR4 / NF-κB
• Unfolded protein response / ER stress (inhibitor) — ER stress
• Wnt / β-catenin canonical signaling (inhibitor) — Wnt/β-catenin (chemopreventive)

Chemical Identifiers

• PubChem CID: 65064
• Formula: C22H18O11
• Molecular weight: 458.37 g/mol
• InChIKey: WMBWREPUVVBILR-WIYYLYMNSA-N
• SMILES: C1[C@H]([C@H](OC2=CC(=CC(=C21)O)O)C3=CC(=C(C(=C3)O)O)O)OC(=O)C4=CC(=C(C(=C4)O)O)O

References

• PMID 11205489