Synonym name: EGCG; 3-O-Galloylepigallocatechin; Teatannin II; Epigallocatechin 3-gallate
Catalogue No.: BP0542
Cas No.: 989-51-5
Formula: C₂₂H₁₈O₁₁
Mol Weight: 458.375
Botanical Source: tea (Thea sinensis), Myrica esculenta, Mallotus japonicus and other plant spp.

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams,up to Kgs, Ton.

EGCG and HIV

There has been some research investigating the benefit of EGCG from green tea in the treatment of HIV infection. One study examined the molecular binding of ECGC to the CD4 receptor molecule on human lymphocytes. The CD4 receptor is the site where the HIV virus attaches to a cell before infecting it. To bind to CD4, HIV uses its own receptor gp120. The study found "clear evidence of high-affinity binding of EGCG to the CD4 molecule" and "inhibition of gp120 binding to human CD4+ T cells." [3][4] The mechanism is very similar to a new class of anti-HIV medications, the entry inhibitors. For reasons not yet understood, EGCG seems to have an inhibitory effect on other steps of the HIV lifecycle, including suppression of reverse-transcriptase concentration and decreased protease kinetics.[5] These effects have only been observed in laboratory studies, not in HIV+ individuals. 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.[6]

References:

Katiyar S, Elmets CA, Katiyar SK (2007). "Green tea and skin cancer: photoimmunology, angiogenesis and DNA repair". J. Nutr. Biochem. 18 (5): 287-96. doi:10.1016/j.jnutbio.2006.08.004. PMID 17049833. 

Neurodegeneration in autoimmune demyelination: Recent mechanistic insights reveal novel therapeutic targets. Orhan Aktas, Sonia Waiczies, Frauke Zipp [1]

Williamson MP, McCormick TG, Nance CL, Shearer WT. Epigallocatechin gallate, the main polyphenol in green tea, binds to the T-cell receptor, CD4: Potential for HIV-1 therapy. J Allergy Clin Immunol. 2006 Dec;118(6):1369-74. Epub 2006 Oct 13. PMID: 17157668

Hamza A, Zhan CG. 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. J Phys Chem B. 2006 Feb 16;110(6):2910-7. PMID: 16471901

Yamaguchi K, Honda M, Ikigai H, Hara Y, Shimamura T. Inhibitory effects of (-)-epigallocatechin gallate on the life cycle of human immunodeficiency virus type 1 (HIV-1). Antiviral Res. 2002 Jan;53(1):19-34. PMID: 11684313

Nance CL, Shearer, WT. Is green tea good for HIV-1 infection? Journal of Allergy and Clinical Immunology Volume 112, Issue 5, November 2003, Pages 851-853. PMID: 14610469.

 

 

 HPLC of Epigallocatechin gallate

 

 

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Epigallocatechin gallate (EGCG), CAS number 989-51-5, is the most abundant and biologically active catechin monomer in green tea, belonging to flavan-3-ol compounds. As an ester derivative formed by (-) - epigallocatechin gallate and gallic acid, EGCG is widely known for its excellent antioxidant capacity. However, in-depth research over the past two decades has revealed that its pharmacological activity extends far beyond this, involving multiple fields such as anti-tumor, anti-inflammatory, neuroprotective, metabolic regulation, and cardiovascular protection. Especially in the prevention and treatment of colon cancer, it exhibits multi-target and multi pathway characteristics. EGCG, as an outstanding representative of natural polyphenols, has become a bridge between traditional beverages and modern precision medicine due to its complex biological effects and relatively clear targets of action. It is also a star molecule for developing new preventive and therapeutic drugs. This article aims to systematically review the chemical properties, sources, pharmacological activities of EGCG, especially its mechanism of action and molecular targets for colon cancer, and objectively evaluate its pharmacological properties, looking forward to its clinical application prospects.

Chemical structure and physicochemical properties

The chemical name of EGCG is (-) - epigallocatechin-3-gallate, with a molecular formula of C22H18O11 and a molecular weight of 458.3750. The core of its structure is the flavan-3-ol skeleton, which is in the cis configuration ("epigenetic" configuration) at positions 2 and 3 of the C ring, and is connected to a galloyl group through an ester bond on the hydroxyl group at position C3. This unique structure endows EGCG with special physicochemical properties and biological activity.

EGCG molecules contain eight phenolic hydroxyl groups, giving them a strong ability to provide protons and electrons, which is the structural basis for their strong antioxidant activity. Its calculated lipid water partition coefficient (LogP) is about 1.98, indicating that it has a certain degree of lipophilicity, but overall it is still a hydrophilic compound. Its topological polar surface area (TPSA) is as high as 197.37 Å ², indicating that its membrane permeability may be limited. Experimental data confirms that the solubility of EGCG in water is approximately 0.3344 mg/mL, which is slightly soluble. These physicochemical parameters collectively determine the pharmacokinetic behavior of EGCG in vivo: low oral bioavailability, rapid metabolism, and selective tissue distribution. For example, its blood-brain barrier permeability is predicted to be "low", which is consistent with its higher polarity and molecular weight, but also suggests that it may require structural modifications or special delivery systems in the treatment of central nervous system diseases. Fortunately, preliminary screening for drug efficacy showed that EGCG had no significant inhibitory effect on hERG potassium channels (hERG inhibition: no), and the Ames test result was 0.6, indicating a low risk of mutagenicity and providing early data support for its safety.

Plant sources and extraction methods

EGCG mainly comes from the tender leaves of Camellia sinensis (L.) O. Ktze. It has the highest content in green tea, usually accounting for 5% -10% of dry weight, much higher than black tea (due to oxidation during fermentation). In addition, trace amounts are also present in some fruits (such as cranberries, blackberries) and nuts.

The extraction of EGCG from tea mainly uses solvent extraction method. Traditional processes use water or ethanol/water mixed solvents for extraction, followed by liquid-liquid extraction and enrichment of catechins using organic solvents such as ethyl acetate. Modern separation and purification technologies have greatly improved efficiency and purity:
1. Column chromatography technology: Use macroporous adsorption resin (such as HP-20), dextran gel (Sephadex LH-20) or reversed silica gel column (C18) for separation, which can effectively remove caffeine, polysaccharide, protein and other impurities.
2. membrane separation technology Preliminary separation and concentration are carried out using ultrafiltration and nanofiltration membranes based on molecular weight.
3. High speed countercurrent chromatography technology As a solid-liquid distribution chromatography without solid carriers, it is particularly suitable for high-purity preparation of thermosensitive polyphenols, avoiding irreversible adsorption.
4. Crystallization method EGCG can form crystals in specific solvent systems (such as ethyl acetate n-hexane) to obtain high-purity products.

Industrial production often combines multiple technologies, such as the combination process of "water extraction membrane concentration resin adsorption solvent elution crystallization", to achieve efficient, green, and large-scale preparation of EGCG.

Pharmacological activity research

The pharmacological activity research of EGCG is extensive and in-depth, and its effects cover almost all major chronic disease fields.

1. Antitumor activity This is the most active field of EGCG research. A large number of in vitro and animal model studies have shown that EGCG can significantly inhibit the growth, proliferation, invasion and metastasis of various tumor cells (such as colon cancer, breast cancer, prostate cancer, lung cancer, liver cancer). Its effect is dose-dependent and time-dependent.
2. Antioxidant and anti-inflammatory activities EGCG is a potent free radical scavenger and metal ion chelating agent that can directly alleviate oxidative stress damage. At the same time, it can downregulate the activity of key inflammatory transcription factors such as nuclear factor kappa B (NF - κ B) and activator protein-1 (AP-1), inhibit the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and various pro-inflammatory cytokines (such as TNF - α, IL-6, IL-1 β), and exert a wide range of anti-inflammatory effects.
3. Neuroprotective activity EGCG can exert a protective effect through the blood-brain barrier. EGCG has shown multiple protective effects in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and cerebral ischemia models, including reducing β - amyloid deposition, inhibiting tau protein hyperphosphorylation, alleviating dopaminergic neuron damage, and inhibiting microglial overactivation.
4. Metabolic regulatory activity EGCG can improve insulin sensitivity and regulate glucose and lipid metabolism by activating AMP activated protein kinase (AMPK), which has potential in the prevention and treatment of type II diabetes, obesity and non-alcoholic fatty liver.
5. Cardiovascular protective activity EGCG can improve endothelial function, inhibit the abnormal proliferation of vascular smooth muscle cells, reduce low-density lipoprotein oxidation, inhibit platelet aggregation, and prevent cardiovascular diseases such as atherosclerosis and hypertension.
6. Other activities EGCG also has various biological activities such as antibacterial, antiviral (such as HIV, influenza virus), anti radiation, and protection of the skin from UV damage.

Mechanism of action and molecular targets

The biological effects of EGCG are not only due to its antioxidant properties, but more importantly, as a polyphenol molecule, it can interact with various proteins, enzymes, receptors, and signaling molecules to regulate complex cellular signaling networks. Taking colon cancer as an example, its anti-tumor effect involves multiple targets and pathways:

1. Inducing cell cycle arrest and apoptosis：

   • Targeting apoptosis regulatory proteins EGCG can downregulate the expression of anti apoptotic proteins B cell lymphoma 2 (BCL2) and myeloid leukemia 1 (MCL1), while possibly upregulating pro apoptotic proteins, disrupting mitochondrial membrane potential, inducing cytochrome C release, activating Caspase cascade reaction, and ultimately leading to cell apoptosis.
   • Inhibit survival signals EGCG can effectively inhibit the phosphorylation and activation of signal transduction and transcription activator 3 (STAT3). STAT3 is a key signaling node that promotes survival and proliferation, and its sustained activation is closely related to the occurrence and development of colon cancer. EGCG suppresses proliferation and promotes apoptosis by inhibiting STAT3 and downregulating its downstream target genes (such as Cyclin D1, BCL2, MCL1).

2. Inhibition of proliferation, invasion and metastasis：

   • Regulating kinase signaling pathway EGCG can inhibit the activity of extracellular signal regulated kinase (MAPK1/ERK) and lymphocyte specific protein tyrosine kinase (LCK) in the mitogen activated protein kinase (MAPK) pathway, interfering with the transmission of pro proliferative signals.
   • Inhibition of nuclear transcription factors EGCG can inhibit the nuclear translocation and DNA binding activity of the subunit RELA (p65) of nuclear factor kappa B (NF - κ B), thereby suppressing the expression of a series of genes related to inflammation, proliferation, invasion, and angiogenesis.
   • Affects metabolic enzymes EGCG is an effective inhibitor of 5-lipoxygenase (ALOX5). ALOX5 is involved in the metabolism of arachidonic acid, and its product leukotriene can promote inflammation and tumor development. Inhibiting ALOX5 helps with anti-inflammatory and anti-tumor effects.

3. Reverse multidrug resistance：

   • Inhibit drug efflux pump EGCG is a regulator of ATP binding cassette transporter B1 (ABCB1/P-glycoprotein). It can competitively bind ABCB1 with anticancer drugs or inhibit its efflux function by consuming ATP, thereby increasing the accumulation of chemotherapy drugs (such as doxorubicin and vincristine) in drug-resistant tumor cells and reversing multidrug resistance.

4. Other direct effects：

   • Inhibition of Topoisomerase I EGCG can directly inhibit the activity of DNA topoisomerase I (TOP1), interfere with DNA replication and repair, leading to DNA damage and cell death.
   • As a molecular chaperone inhibitor EGCG can bind to the N-terminal domain of heat shock protein 90 (Hsp90), inhibit its ATPase activity, and cause ubiquitination degradation of its client proteins (such as AKT, RAF-1, HIF-1 α), which are key molecules in promoting survival and adaptation signals. Their degradation can effectively inhibit tumor growth.
   • Activate energy sensor AMPK EGCG can directly or indirectly activate AMPK (composed of subunits such as PRKAA1) by increasing the intracellular AMP/ATP ratio or calcium ion levels. Activated AMPK can inhibit the mammalian rapamycin target protein (mTOR) pathway, suppress protein synthesis and cell growth, while promoting autophagy and fatty acid oxidation, playing a central role in metabolic regulation and tumor inhibition.

In summary, the role of EGCG in colon cancer is like a carefully planned "multi-target attack", forming a three-dimensional anti-tumor network from inducing apoptosis, inhibiting proliferation, anti-inflammatory, reversing drug resistance to interfering with metabolism.

Evaluation of drug properties and pharmacokinetics

Although EGCG has excellent in vitro activity, its pharmacological properties, especially oral bioavailability, are the main bottleneck restricting its clinical translation.

• absorb After oral administration, the absorption rate of EGCG in the gastrointestinal tract is low (<5%). Its absorption in the intestine includes passive diffusion and carrier mediated active transport (such as monocarboxylate transporters). Both the acidic environment in the stomach and the alkaline environment in the small intestine may lead to structural isomerization (conversion to less active GCG) or hydrolysis.
• distribution After absorption, EGCG rapidly binds extensively to plasma proteins such as albumin and fibrinogen, affecting its free concentration and tissue distribution. Its blood-brain barrier permeability is low, but in some inflammatory or tumor tissues, there may be a certain degree of accumulation due to increased vascular permeability.
• Metabolism EGCG undergoes extensive phase II metabolism in the body, mainly through glucuronidation and sulfation in the liver and intestines, generating corresponding complexes. In addition, the gut microbiota can also break it down into small molecule phenolic acids (such as 5- (3 ', 4', 5 '- trihydroxyphenyl) - γ - valerolactone).
• excretion EGCG and its metabolites are mainly excreted through urine and bile, with a short half-life (about 3-4 hours).
• Stability EGCG is unstable at physiological pH (neutral or weakly alkaline) and temperature, and is prone to oxidation, polymerization, and degradation, which further reduces its bioavailability and in vivo activity.

To improve the pharmacological properties of EGCG, current research strategies include:
1. Structural modification Methylation, esterification, or prodrug preparation of phenolic hydroxyl groups to improve stability, lipid solubility, and membrane permeability.
2. New delivery system Develop nanoparticles (liposomes, polymer nanoparticles), microemulsions, phospholipid complexes, cyclodextrin inclusion complexes, etc. to protect EGCG from degradation, enhance its targeting, control its release, and improve its bioavailability.
3. combination therapy Combined with substances such as vitamin C and piperine, it can inhibit the metabolism of EGCG and increase its plasma concentration.

Clinical application prospects and prospects

At present, EGCG mainly exists in the form of dietary supplements as a preventive health product. Its clinical application development is moving towards two main directions:

1. Disease Prevention and Health Management Based on its excellent safety and extensive health benefits, high-purity and standardized EGCG preparations have enormous market potential in fields such as cancer chemoprevention, early intervention of neurodegenerative diseases, and management of metabolic syndrome. Large scale and long-term population intervention studies are key to confirming their preventive effects.
2. As a therapeutic drug development：
   • adjuvant therapy Combined with existing chemotherapy and targeted drugs, utilizing its multi-target properties to enhance efficacy, reduce side effects, and reverse drug resistance. For example, in the treatment of colon cancer, studies on the combination of EGCG with drugs such as 5-fluorouracil and oxaliplatin have shown synergistic effects.
   • New drug development Using EGCG as the lead compound, structural optimization is carried out to develop derivatives or analogues with higher stability, selectivity, and bioavailability. For example, EGCG's esterification prodrug or analogs designed for specific targets such as Hsp90.
   • Local medication Developing topical formulations for skin diseases such as acne, psoriasis, and photoaging by utilizing their anti-inflammatory, antioxidant, UV resistant, and antibacterial properties can avoid oral bioavailability issues.

The future research focus should include: ① using systems biology and computational chemistry methods to more accurately elucidate its in vivo action network and direct targets; ② Conduct rigorously designed and sufficiently scaled Phase II/III clinical trials to confirm their efficacy and optimal dosage regimen in specific diseases such as colon adenomas and mild cognitive impairment; ③ Deeply explore its individualized application and study the impact of genetic polymorphism (such as differences in metabolic enzymes and transporter genes) on the efficacy and toxicity of EGCG; ④ Develop smarter and more efficient targeted delivery systems to achieve precise enrichment of disease sites.

Conclusion

Epigallocatechin gallate (EGCG), as a chemical masterpiece gifted by nature, has grown from a simple tea polyphenol to a focal molecule in modern pharmacological research, and its history is remarkable. Based on its multi hydroxyl chemical structure, it plays multiple biological roles such as antioxidant, signal regulation, and protein interaction, especially demonstrating the unique advantage of a "multi-target regulatory network" in combating complex diseases such as colon cancer. Despite its inherent pharmaceutical defects, such as low oral bioavailability and metabolic instability, which pose challenges to direct drug development, this has precisely sparked a research boom in dosage form innovation, structural modification, and combination strategies. The research paradigm of EGCG provides valuable references for the development of other natural products, from prevention to treatment, from adjuvant drugs to new drug lead compounds. With the deep integration of modern science and technology, especially delivery technology and precision medicine, EGCG is expected to break through bottlenecks and truly transform from a health guardian in daily drinking cups to a clinical treatment weapon, playing a more practical and important role in the human journey to fight chronic diseases. Continuous and in-depth research on it is not only about uncovering the value of individual compounds, but also about exploring the mysteries of the dialogue between complex life systems and natural chemicals.