Product name: Catechin gallate
Synonym name: (-)-Catechin gallate
Catalogue No.: BP0323
Cas No.: 130405-40-2
Formula: C₂₂H₁₈O₁₀
Mol Weight: 442.376
Botanical Source: Green Tea
Physical Description:
Type of Compound: Polyphenols

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

Description:

Catechin gallate is a minor constituent in green tea catechins, it inhibits the activity of COX-1 and COX-2 enzymes. Catechin gallate (IC50=53 microM) shows cytotoxicity against the colorectal adenocarcinoma cell line HCT116, it also exhibits strong anti-proliferative and anti-inflammatory activities on pancreatic ductal adenocarcinoma (PDAC) cells. Catechin 3-gallate is a good inhibitor of maltase, with IC50 values of 62 uM, it inhibits both α-glucosidases and rabbit glycogen phosphorylase (GP) in vitro and in cell culture, would contribute to the protection or improvement of type 2 diabetes.

References:

In vitro cytotoxicity of (-)-catechin gallate, a minor polyphenol in green tea.[Pubmed: 17606338]

Toxicol Lett. 2007 Jul 10;171(3):171-80.

The cytotoxicity of (-)-Catechin gallate(CG), a minor polyphenolic constituent in green tea, towards cells derived from tissues of the human oral cavity was studied.

METHODS AND RESULTS:

The sequence of sensitivity to (-)-Catechin gallate(CG) was: immortalized epithelioid gingival S-G cells>tongue squamous carcinoma CAL27 cells>salivary gland squamous carcinoma HSG cells>>normal gingival HGF-1 fibroblasts. Further studies focused on S-G cells, the cells most sensitive to (-)-Catechin gallate(CG). The response of the S-G cells to (-)-Catechin gallate(CG) was dependent on the length of exposure, with midpoint cytotoxicity values of 127, 67 and 58muM (-)-Catechin gallate(CG) for 1-, 2- and 3-day exposures, respectively. The sequence of sensitivity of the S-G cells to various green tea catechins was characterized as follows: (-)-Catechin gallate(CG), epicatechin gallate (ECG)>epigallocatechin gallate (EGCG)>epigallocatechin (EGC)>>epicatechin (EC), catechin (C). The cytotoxicity of (-)-Catechin gallate(CG), apparently, was not due to oxidative stress as it was a poor generator of H(2)O(2) in tissue culture medium, had no effect on the intracellular glutathione level, its cytotoxicity was unaffected by catalase, and it did not induce lipid peroxidation. However, (-)-Catechin gallate(CG) did enhance Fe(2+)-induced, lipid peroxidation. (-)-Catechin gallate(CG)-induced apoptosis was detected by nuclear staining, both with acridine orange and by the more specific TUNEL procedure. The lack of caspase-3 activity in cells exposed to (-)-Catechin gallate(CG) and the detection of a DNA smear, rather than of discrete internucleosomal DNA fragmentation, upon agarose gel electrophoresis, suggest, possibly, that the mode of cell death was by a caspase-independent apoptotic pathway.

CONCLUSIONS:

The overall cytotoxicity of (-)-Catechin gallate(CG) was similar to its epimer, ECG and both exhibited antiproliferative effects equivalent to, or stronger than, EGCG, the most abundant catechin in green tea.

In vitro inhibition of α-glucosidases and glycogen phosphorylase by catechin gallates in green tea.[Reference: WebLink]

Food Chem.,2010,122(4):1061-6.

We investigated in vitro inhibition of mammalian carbohydrate-degrading enzymes by green tea extract and the component catechins, and further evaluated their inhibitory activities in cell cultures.

METHODS AND RESULTS:

The extract showed good inhibition toward rat intestinal maltase and rabbit glycogen phosphorylase (GP) b, with IC50 values of 45 and 7.4 μg/ml, respectively. The polyphenol components, catechin 3-gallate (CG), gallocatechin 3-gallate (GCG), epicatechin 3-gallate (ECG), and epigallocatechin 3-gallate (EGCG), were good inhibitors of maltase, with IC50 values of 62, 67, 40, and 16 μM, respectively, and EGCG also showed good inhibition toward maltase expressed on Caco-2 cells, with an IC50 value of 27 μM. The ungallated catechins, such as catechin, gallocatechin (GC), epicatechin (EC), and epigallocatechin (EGC), showed no significant inhibition toward GP b, whereas the gallated catechins CG, GCG, ECG, and EGCG inhibited the enzyme, with IC50 values of 35, 6.3, 27, and 34 μM. From multiple inhibition studies by Dixon plots, GCG appears to bind a new allostelic site, the indole inhibitor site. These gallated catechins also inhibited glucagon-stimulated glucose production dose-dependently, with IC50 values ranging from 33 to 55 μM.

CONCLUSIONS:

Dietary supplementation with these gallated catechins or the green tea extract containing them, which inhibits both α-glucosidases and GP in vitro and in cell culture, would contribute to the protection or improvement of type 2 diabetes.

HPLC of Catechin gallate

HNMR of Catechin gallate

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

Introduction/Overview

Natural products have long been an important source of innovative drug discovery, among which polyphenolic compounds have attracted much attention due to their wide range of biological activities. Catechin gallate (CG), as an ester derivative formed by the combination of catechins and gallic acid, is a key functional component in plants such as tea. Its CAS number is 130405-40-2, usually referring to (+) - catechin-3-O-gallate, which is the enantiomer of (-) - catechin-3-O-gallate. Early studies have revealed that it can effectively inhibit cyclooxygenase-1 (COX-1), with an IC50 value of 1.4 μ M, indicating its anti-inflammatory potential. In recent years, with the deepening of research, especially the continuous exploration of its multiple target effects in the field of antiviral, catechin gallate has transformed from an ordinary tea polyphenol member to a promising lead compound in pharmacological research. The purpose of this article is to systematically review the chemical properties, plant sources, pharmacological activities, mechanisms of action, and medicinal properties of catechin gallate, and to look forward to its clinical application prospects, in order to provide comprehensive academic references for the in-depth research and development of this compound.

Chemical structure and physicochemical properties

The chemical essence of catechin gallate is the gallate ester formed by the ester bond between flavan-3-ol (catechin) and gallic acid. Specifically, it is the condensation dehydration of the carboxyl group of gallic acid with the (3R) - hydroxyl group on the C ring of (-) - catechins to form (-) - catechin-3-O-gallate ester. Its molecular formula is C22H18O10 and its molecular weight is 442.3760. The structure contains two benzene rings (A ring and B ring) and one oxygen-containing heterocyclic ring (C ring), as well as the benzene ring of the galloyl group, which gives it multiple phenolic hydroxyl groups, making it a typical polyphenolic compound.

This structure determines its unique physicochemical properties. Its calculated lipid water partition coefficient (LogP) is about 2.25, indicating that it has a certain lipophilicity, but the large number of polar hydroxyl groups in the molecule (with a topological polar surface area TPSA of up to 177.14 Å ²) endow it with hydrophilicity. The theoretical water solubility is about 0.27 mg/mL, which is slightly soluble. This amphiphilicity has a significant impact on its biofilm penetration and bioavailability. The compound is difficult to penetrate the blood-brain barrier (predicted as low permeability), which limits its direct effects on central nervous system diseases. In the preliminary safety assessment, the hERG inhibition risk was negative, and the Ames test result was 0.6 (usually considered negative if less than 1.5), indicating a low risk of mutagenicity and providing preliminary safety evidence for subsequent development.

Plant sources and extraction methods

Epicatechin gallate is widely present in various plants, especially in the Theaceae family. Tea is its most abundant and common source, detected in green tea, oolong tea, black tea, etc. Among them, unfermented green tea usually has a higher content. It does not exist in a single form, but as a component or metabolic precursor of complex catechin mixtures such as epigallocatechin gallate EGCG, epigallocatechin gallate ECG, etc. In addition, it is also distributed in some medicinal plants such as Euphorbiaceae and Rosaceae.

The extraction method follows the general principles of plant polyphenol extraction. Common solvent extraction methods use ethanol, methanol, or acetone aqueous solutions of different concentrations for extraction or heating reflux. To obtain higher purity CG, it is often necessary to combine multiple separation and purification techniques. After the crude extract is extracted and enriched by organic solvent (such as ethyl acetate), it can be preliminarily separated by column chromatography in turn. Common stationary phases include silica gel, polyamide, dextran gel (such as Sephadex LH-20), etc. The final high-purity preparation relies on high-performance liquid chromatography, especially preparative HPLC, using a C18 reverse phase chromatography column and gradient elution with methanol water or acetonitrile water (often containing small amounts of formic acid or acetic acid to improve peak shape) as the mobile phase. In recent years, some green extraction techniques such as ultrasound assisted extraction, microwave-assisted extraction, and supercritical CO2 extraction have also been explored to improve extraction efficiency and selectivity.

Pharmacological activity research

Epicatechin gallate exhibits diverse pharmacological activities, and its research has expanded from anti-inflammatory to antiviral, antioxidant, anti-tumor and other fields.

1. anti-inflammatory activity Its inhibition of COX-1 activity (IC50 1.4 μ M) is the classic mechanism basis for its anti-inflammatory effect. COX-1 is a constitutive cyclooxygenase involved in maintaining physiological prostaglandin synthesis, and its overactivation is associated with inflammation and pain. The strong inhibition of COX-1 by CG suggests that it may have anti-inflammatory and analgesic potential similar to nonsteroidal anti-inflammatory drugs. In addition, studies have shown that it can inhibit the production of inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), and downregulate the expression of inducible nitric oxide synthase (iNOS) and COX-2.

2. Antiviral activity (core activity)This is currently the most focused area of CG research. It has been found to have inhibitory effects on various viruses, involving multiple targets:

   • Herpesvirus Regarding herpes simplex virus (HSV), CG may inhibit virus replication by interfering with the functions of essential proteins for virus replication, such as UL42 (DNA polymerase helper subunit), UL54 (ICP27, transcription regulator), and thymidine kinase (TK). It may also have a similar effect on cytomegalovirus (CMV).
   • Human Immunodeficiency Virus (HIV)CG has been reported to inhibit the activity of HIV-1 protease (HIV1-PR), which is crucial for virus maturation. At the same time, it can also act on viral integrase (INT), interfering with the integration of viral DNA into the host genome. More meaningfully, as a potential regulator of CCR5 and CXCR4, it may block HIV from utilizing these co receptors to enter host cells, providing a multi link strategy for inhibiting HIV.
   • Other viruses Its antiviral spectrum may be broader, and related targets include myeloperoxidase (MPO), which is associated with inflammatory damage caused by certain viral infections.

3. antioxidant activity As a polyphenol, CG is an effective free radical scavenger and metal ion chelating agent. Its multiple phenolic hydroxyl groups can provide hydrogen atoms or electrons, neutralize reactive oxygen species (ROS) and reactive nitrogen species (RNS), and protect cells from oxidative stress damage, which is considered the common basis for many of its downstream pharmacological effects, such as anti-inflammatory, anti-aging, and neuroprotection.

4. Antitumor activity Preliminary studies have shown that CG can inhibit the proliferation of various cancer cells, induce apoptosis and cell cycle arrest. The mechanism may be related to regulating the Bcl-2/Bax protein ratio, activating the caspase cascade, inhibiting the NF - κ B signaling pathway, and the aforementioned antioxidant and anti-inflammatory effects.

5. Other activities There are also research reports that CG has potential activities such as antibacterial, cardiovascular protection, and improvement of metabolic syndrome.

Mechanism of action and molecular targets

The multiple pharmacological activities of catechin gallate stem from its interactions with various biomolecules, and its mechanism of action is complex and multi-target.

1. Enzyme inhibition This is its most direct mode of action.

   • COX-1 inhibition By binding to the active site of COX-1 in a competitive or non competitive manner, arachidonic acid is prevented from being converted into prostaglandin precursors, thereby inhibiting the synthesis of prostaglandin inflammatory mediators.
   • Viral enzyme inhibition Directly bind to the active center of HIV-1 protease or integrase, inhibit its catalytic function, and block key steps in the virus lifecycle. It may also have a similar inhibitory effect on enzymes such as TK in HSV.

2. Receptor interaction/interference：

   • Chemokine receptor antagonism Its structure may allow it to bind to the extracellular domains of HIV co receptors CCR5 and CXCR4, thereby physically blocking the binding of virus envelope glycoprotein gp120 to the receptor, preventing the fusion and entry of the virus into the cell membrane. This is an important potential mechanism for its prevention of HIV infection.

3. Transcription and signal pathway regulation：

   • Inhibition of NF - κ B pathway Oxidative stress and inflammatory factors can activate the NF - κ B pathway. CG reduces ROS through its antioxidant activity and may directly interfere with IKK complexes or prevent the degradation of I κ B α, thereby inhibiting NF - κ B nuclear translocation and downregulating the expression of inflammatory factors (such as TNF - α, IL-6), iNOS, and COX-2 genes regulated by it.
   • MAPK pathway regulation May affect the phosphorylation status of MAPK signaling molecules such as ERK, JNK, and p38, thereby regulating cell proliferation, differentiation, and apoptosis.

4. Direct interaction and interference：

   • Binding with viral proteins In addition to the enzyme active center, CG may also interfere with its interaction with viral DNA or other viral proteins by binding to non enzyme proteins such as UL42 and ICP27 of HSV, disrupting the assembly of viral transcription and replication complexes.
   • Membrane interaction Its amphiphilic structure may allow it to insert into the viral envelope or cell membrane, alter membrane fluidity, and affect the fusion process between the virus and the cell.

Evaluation of drug properties and pharmacokinetics

Although catechin gallate exhibits significant in vitro activity, its pharmacological properties face challenges, with pharmacokinetic properties being the main bottleneck.

1. absorb After oral administration, its absorption rate in the gastrointestinal tract may not be high. Ester bonds are easily hydrolyzed by esterases in the digestive system, releasing (-) - catechins and gallic acid, leading to reduced absorption of the prototype drug. The absorbed portion may be carried out through passive diffusion and certain transport proteins.

2. distribution The high molecular weight and strong polarity may result in a higher plasma protein binding rate, limiting its free distribution. As mentioned earlier, its ability to penetrate the blood-brain barrier is weak and mainly distributed in organs with abundant blood supply.

3. Metabolism CG is a substrate for metabolism. In addition to gastrointestinal hydrolysis, it undergoes extensive phase II metabolism in the liver and intestines, mainly glucuronidation and sulfation, forming corresponding complexes. These metabolic processes are rapid and thorough, which is the main reason for their short half-life and low exposure to prototype drugs in the body. The cytochrome P450 enzyme system may also be involved in its minor phase I metabolism.

4. excretion Metabolites are mainly excreted in urine through the kidneys, and some prototype drugs and metabolites can also be excreted in feces through bile.

5. Optimization direction of drug properties：

   • Structural modification Methylation, glycosylation or preparation of prodrugs (such as esterification, preparation of phospholipid complexes) of phenolic hydroxyl groups to improve their lipid solubility, membrane penetration and metabolic stability.
   • Formulation innovation Develop nano formulations (such as liposomes, nanoparticles, micelles), microemulsions, cyclodextrin inclusion complexes, etc. to enhance their solubility, protect them from enzymatic hydrolysis, achieve targeted delivery, and control release.
   • route of administration Explore local administration (such as skin anti HSV), inhalation administration (for respiratory viruses), or injection administration (to address solubility and stability issues) to avoid first pass effects.

Clinical application prospects and prospects

The clinical application prospects of catechin gallate ester are broad, but the road ahead is long.

1. Potential application areas：

   • antiviral therapy As a multi-target antiviral lead compound, especially targeting HSV, HIV, and potential novel enveloped viruses (such as by interfering with CCR5/CXCR4). It can be considered as a local medication for the treatment of HSV skin and mucosal infections, or as a supplementary component of HIV cocktail therapy.
   • Anti inflammatory and analgesic effects Based on its COX-1 inhibitory properties, it can be used to develop natural source drugs or health supplements for the treatment of mild to moderate inflammation and pain, which may have better antioxidant synergistic effects than traditional NSAIDs.
   • Adjuvant tumor therapy Its antioxidant, anti-inflammatory, and pro apoptotic properties make it possible to use it as a chemopreventive agent or in combination with conventional chemotherapy/radiotherapy to enhance efficacy and reduce side effects.
   • Functional foods and cosmetics As a potent antioxidant, it is widely used in health foods, beverages, and cosmetics that resist aging and photodamage.

2. challenges faced：

   • Low bioavailability This is the biggest obstacle to pushing it into clinical practice.
   • Complexity of mechanism of action Multi targeting is both advantageous and may lead to off target effects and unpredictable in vivo interactions, requiring more precise mechanism elucidation.
   • Source and Cost Extracting high-purity CG from plants in large quantities is costly, and the chemical synthesis steps are cumbersome, requiring the development of efficient and economical large-scale preparation processes.
   • Lack of preclinical and clinical research Currently, the vast majority of research remains at the cellular and animal levels, lacking systematic toxicology, pharmacokinetics, and efficacy clinical trial data.

3. Future research directions：

   • Using computer-aided drug design and structural biology methods, analyze the precise binding patterns between CG and key targets such as HIV1-PR and CCR5, and guide rational structural optimization.
   • Strengthen pharmaceutical research based on novel drug delivery systems and improve their pharmacokinetic behavior.
   • Conduct standardized preclinical safety assessments (long-term toxicity, reproductive toxicity, etc.) and exploratory clinical studies to accumulate human data.
   • Explore its synergistic effects with other drugs and develop combination therapy plans.

Conclusion

As a natural polyphenolic compound derived from tea, catechin gallate exhibits remarkable pharmacological activity in anti-inflammatory, especially antiviral fields due to its unique chemical structure and multi-target mechanism of action. From inhibiting COX-1 to interfering with HIV entry and replication, its spectrum of action reveals the enormous potential of natural products in addressing complex diseases. However, its poor pharmacokinetic properties, such as low oral bioavailability and rapid metabolism, are currently the main constraints for its conversion into clinical drugs. Future research should focus on overcoming these pharmaceutical bottlenecks through medicinal chemistry and pharmacology methods, and further elucidate their in vivo mechanisms of action and safety. With the deepening of interdisciplinary research, catechin gallate is expected to gradually develop from an active phytochemical molecule to a candidate drug or important lead compound skeleton with clear clinical application value, providing new strategies and options for the prevention and treatment of infectious diseases, inflammation and related diseases.