Product name: Epicatechin
Synonym name: Epicatechol; (-)-Epicatechin;Teacatechin I; Acacatechin; Kakaol; Colatein
Catalogue No.: BP0538
Cas No.: 490-46-0
Formula: C₁₅H₁₄O₆
Mol Weight: 290.271
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.




Chengdu Biopurify Phytochemicals Ltd. is a leading company in the research, development, manufacture and marketing of High Quality Phytochemicals and Extracts(especially Active Ingredients from Traditional Chinese Medicine，TCM), Natural Active Pharmaceutical Ingredients worldwide.
The main services:
A. Supply active ingredients and reference standards of TCM, from mgs to kgs scale
B. Custom extraction and purification, target Herb Active Ingredients
C. Custom synthesis and semi-synthesis for Natural Active Ingredients
D. CR(contract research), CM(contract manufacture) and PD(process development) services from lab scale, pilot scale to commercial scale(GMP is also available)
E. TCM compounds library for drug screen,more than 3000 compounds available, many of them are rare and unique.

HPLC of Epicatechin 

NMR of Epicatechin 

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

Introduction/Overview

Epicatechin (EC), also known as (2R, 3R) -2- (3,4-dihydroxyphenyl) -3,4-dihydro-2H-1-benzopyran-3,5,7-triol, is a widely present flavan-3-alcohol compound in nature. It is one of the main bioactive components in various plant-based foods such as tea, cocoa, grapes, and apples. Its CAS number is 490-46-0, and it usually exists in the form of (±) - epicatechin (racemic) or a single enantiomer. As an important member of the catechin family, epicatechin has long been highly regarded for its excellent antioxidant capacity. Modern pharmacological research continuously reveals its extensive biological activities beyond antioxidant, including anti-inflammatory, anti hyperuricemia, cardiovascular protection, neuroprotection, and potential anti-tumor effects. Especially its activity as a xanthine oxidase inhibitor (IC50 of 982.14 μ M) provides direct scientific basis for its application in the study of hyperuricemia and gout. With the development of systems biology and molecular pharmacology, the target network of epicatechin is becoming increasingly clear, especially playing a key role in the nuclear factor E2 related factor 2 (NRF2/NFE2L2) signaling pathway and downstream antioxidant enzyme system closely related to oxidative stress damage. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, molecular mechanisms of action, pharmacological evaluation, and clinical application prospects of catechins, in order to provide comprehensive academic references for the in-depth development and transformation research of this natural product.

Chemical structure and physicochemical properties

Epicatechins belong to flavan-3-ol compounds, with a molecular formula of C15H14O6 and a molecular weight of 290.2710. Its basic structure consists of a benzodihydropyran (C ring) core, with the A ring being a meta phenyltriphenylene type (5,7-dihydroxy) and the B ring being a catechol type (3 ', 4' - dihydroxy). The 2nd and 3rd carbon atoms of the C ring are chiral centers with an R configuration. Common epicatechins usually refer to (-) - epicatechins, whose 2R and 3R configurations are the main contributors to their biological activity; And its diastereomers are (-) - epigallocatechin gallate (EGC) or (+) - catechin. The (±) - epicatechin mentioned in the article is a racemic mixture.

In terms of physical and chemical properties, epicatechin is usually a white to off white crystalline powder. Its lipid water partition coefficient (LogP) is 0.9684, indicating that it has a certain degree of lipophilicity, but overall it still leans towards hydrophilicity. The topological polar surface area (TPSA) is 110.3800 Å ², reflecting the strong polarity brought by multiple hydroxyl groups in the molecule. Its water solubility data is 0.7466 (usually measured in mg/mL or g/L, depending on the specific system), indicating that it has moderate solubility in water, which is beneficial for its absorption and distribution in organisms. However, its blood-brain barrier permeability is predicted to be 'low', which may limit its direct therapeutic effect on central nervous system diseases. The preliminary safety evaluation shows that the risk of hERG channel inhibition is "no", and the Ames test result is 0.0 (usually indicating no mutagenicity), indicating that it has good cardiac safety and genotoxic safety profile.

Plant sources and extraction methods

Epicatechins are widely distributed in the plant kingdom and are secondary metabolites of various common edible and medicinal plants.
1. Main plant sources：
* tea Especially green tea and unfermented tea are rich in various catechins, and epicatechin is one of them.
* cocoa bean The high content of epicatechin in dark chocolate is considered a key component for its cardiovascular benefits.
* Grapes and wine Grape seeds and grape skins are rich in anthocyanins (polymerized from monomers such as epicatechin), and red wine also contains a certain amount of free epicatechin.
* Apples and berries Apple peels, blueberries, cranberries and other fruits are important sources of epicatechin in daily diet.
* medicinal plants As mentioned in the title sterculia lychnophora（Sterculia lychnophora）， The extract of its seeds contains epicatechin, which provides some modern pharmacological explanations for its traditional use in clearing heat, moistening the lungs, and detoxifying the throat. In addition, it has also been detected in medicinal plants such as Ginkgo biloba leaves and Forsythia suspensa.

1. Extraction and Separation Methods：
   Solvent extraction is commonly used to extract epicatechin from plant materials. Common solvents include water, methanol, ethanol, acetone, and their aqueous solutions. In order to improve extraction efficiency and selectivity, modern technologies such as:
   • Ultrasonic assisted extraction Using cavitation effect to destroy cell walls and accelerate solute release.
   • Microwave assisted extraction By microwave heating, the temperature and pressure inside the cell rapidly increase, promoting the dissolution of target components.
   • Supercritical fluid extraction(Commonly used CO2): Suitable for thermosensitive components, but requires the addition of entrainers (such as ethanol) to increase the solubility of polyphenolic substances.
     After filtration and concentration, the crude extract needs to be further purified to obtain high-purity epicatechin. Common purification techniques include:
   • column chromatography: Silica gel, polyamide, dextran gel (such as Sephadex LH-20) and other fillers are used for separation. Sephadex LH-20 is particularly suitable for the classification of polyphenolic compounds.
   • High performance liquid chromatography This is the most effective method for preparing high-purity epicatechin monomers, especially preparative HPLC.
   • High-speed countercurrent chromatography A liquid-liquid distribution chromatography that does not require a solid phase carrier, avoids irreversible adsorption, and is suitable for large-scale preparation.

Pharmacological activity research

Epicatechins exhibit diverse pharmacological activities, and their core role is closely related to regulating redox balance.
1. Antioxidant and anti-inflammatory activities This is the most fundamental and important activity of epicatechin. It can directly scavenge free radicals such as DPPH and ABTS, chelate metal ions such as Fe2+and Cu2+, and prevent their catalytic production of hydroxyl radicals. More importantly, it can indirectly exert strong antioxidant effects by activating the cell's own antioxidant defense system (see next section for details). The anti-inflammatory effect is closely related to antioxidant activity. Epicatechins can reduce the production of inflammatory mediators such as tumor necrosis factor alpha (TNF - α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) by inhibiting inflammatory signaling pathways such as nuclear factor kappa B (NF - κ B).
2. Anti hyperuricemia and gout related activity Epicatechin is a competitive inhibitor of xanthine oxidase (XO). XO is a key enzyme in the production of uric acid, catalyzing the conversion of hypoxanthine to xanthine and then to uric acid. Epicatechins have potential therapeutic effects on hyperuricemia and gout by inhibiting XO activity and reducing uric acid production. Its IC50 is 982.14 μ M, although its activity is weaker than classical drugs such as allopurinol, its natural and multi-target properties make it an attractive adjuvant or preventive strategy.
3. Cardiovascular protective effect Numerous studies have confirmed that epicatechin can improve endothelial function, promote nitric oxide (NO) production, and lower blood pressure; Inhibit the oxidation of low density lipoprotein (LDL) and reduce the formation of atherosclerotic plaque; It also has anti platelet aggregation and anti thrombotic effects.
4. Neuroprotective effect Although the blood-brain barrier permeability is low, epicatechin can still exert neuroprotective effects through indirect mechanisms such as regulating peripheral inflammation and improving cerebrovascular function, or at low concentrations. Research has shown that it may improve cognitive function, slow down the progression of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, by inhibiting β - amyloid protein aggregation, reducing neuroinflammation, and mitochondrial dysfunction.
5. Other activities This also includes the potential to improve insulin resistance, protect the liver (against liver fibrosis), resist tumors (induce cell cycle arrest and apoptosis), and enhance exercise endurance.

Mechanism of action and molecular targets

The pharmacological effects of epicatechin are not achieved through a single target, but through a complex multi-target network, in which Pathway related to antioxidant damage Occupies a central position.

1. Core target: NRF2/KEAP1 signaling pathway：

   • NRF2 Nuclear factor E2 related factor 2, encoded by the NFE2L2 gene, is a key transcription factor that regulates cellular oxidative stress response. In the resting state, NRF2 binds to its cytoplasmic inhibitory protein KEAP1 and is degraded by ubiquitination. When stimulated by electrophilic substances such as epicatechin or oxidative stress, the conformation of KEAP1 changes and releases NRF2.
   • mechanism of action Free NRF2 translocates to the nucleus and binds to antioxidant response elements (ARE), initiating the transcriptional expression of a series of phase II detoxifying enzymes and antioxidant proteins. Epicatechins have been shown to effectively activate NRF2.

2. Downstream key antioxidant/detoxifying enzyme targets：

   • Heme oxygenase-1 Encoded by the HMOX1 gene. HMOX1 breaks down hemoglobin to produce biliverdin (a strong antioxidant), carbon monoxide, and iron ions, which are important cell protective enzymes.
   • Superoxide Dismutase Including intracellular SOD1(Cu/Zn SOD) and mitochondria SOD2（Mn-SOD）， It is the first line of defense for clearing superoxide anion radicals.
   • catalase Encoded by the CAT gene, it is responsible for catalyzing the decomposition of hydrogen peroxide into water and oxygen, and preventing the generation of hydroxyl radicals.
   • Glutathione peroxidase 1 Encoded by the GPX1 gene, it utilizes reduced glutathione (GSH) to reduce hydrogen peroxide and lipid peroxides, maintaining cellular redox homeostasis.
     Epicatechins significantly upregulate the expression of the aforementioned genes by activating NRF2, thereby systematically enhancing the antioxidant defense ability of cells and resisting endogenous and exogenous oxidative damage.

3. Other important molecular mechanisms：

   • xanthine oxidase inhibitor Directly binding to the active site of XO, competitively inhibiting its catalytic activity, is the direct molecular basis of its uric acid lowering effect.
   • Regulating the inflammatory signaling pathway Inhibit the activation of NF - κ B and reduce the expression of inflammatory factors; Meanwhile, activated NRF2 can also engage in cross talk with NF - κ B, negatively regulating inflammatory responses.
   • Affects cell survival and apoptosis pathways It can activate survival promoting signals such as PI3K/Akt and ERK, regulate Bcl-2 family proteins, and inhibit cell apoptosis through the mitochondrial pathway.
   • Epigenetic regulation Recent studies have found that epicatechin may regulate the long-term expression of related genes by affecting histone modification and DNA methylation.

Evaluation of drug properties and pharmacokinetics

Although epicatechin has a wide range of biological activities, its development as a drug still faces some challenges in drug formulation.

1. Absorption, distribution, metabolism, and excretion：

   • absorb After oral administration, it is mainly absorbed in the small intestine. Its multiple phenolic hydroxyl structures result in limited lipid solubility and low absolute bioavailability (usually<10%). Taking it with food may affect its absorption rate and degree.
   • distribution After absorption, it is widely distributed throughout the body, but due to its strong first pass effect and rapid metabolism, the concentration of the original drug in the plasma is usually low. Its high TPSA and predicted low blood-brain barrier permeability limit its distribution in the central nervous system.
   • Metabolism Epicatechins undergo extensive metabolism in the body.II binding reaction is its main metabolic pathway Including glucuronidation, sulfation, and methylation, they mainly occur in the liver and intestines, generating corresponding complexes. In addition, the gut microbiota can break it down into smaller phenolic acid compounds (such as hippuric acid, hydroxyphenylpropionic acid, etc.), which may also contribute to its biological activity.
   • excretion Metabolites are mainly excreted through urine, with some entering the intestine through bile and excreted with feces. The excretion of the prototype drug is minimal.

2. Advantages and challenges of pharmaceutical properties：

   • Advantage High safety (Ames negative, no hERG inhibition), wide source, relatively low cost, multi-target mechanism of action, suitable as a preventive or adjuvant therapeutic agent.
   • challenge：
     • Low oral bioavailability This is its main development bottleneck, due to solubility, intestinal permeability, and strong first pass metabolism.
     • chemical stability Catechin compounds are prone to isomerization (such as EC conversion to catechins) and oxidative polymerization in alkaline, high temperature, and high oxygen environments, which can affect their potency.
     • Metabolism is too fast Short half-life in the body, frequent administration is required to maintain effective concentration.

3. Formulation improvement strategy：
   To enhance its medicinal properties, researchers have developed various delivery systems:

   • nano-formulation Such as liposomes, nanoemulsions, solid lipid nanoparticles, polymer nanoparticles, etc., can improve solubility, protect them from degradation, enhance intestinal absorption, and potentially achieve targeted delivery.
   • Prodrug strategy By chemically modifying phenolic hydroxyl groups, ester or ether prodrugs are made to improve lipid solubility and metabolic stability, and the original drug is released after hydrolysis in vivo.
   • Phospholipid complex Forming complexes with phospholipids significantly improves their lipid solubility and biofilm permeability.
   • Eutectic/co amorphous Forming eutectic or amorphous systems with other medicinal excipients to improve solubility and dissolution rate.

Clinical application prospects and prospects

Epicatechins have a broad prospect in transitioning from a dietary component to a clinical therapeutic agent, but the path needs to be cautiously explored.

1. Potential clinical application directions：

   • Adjuvant therapy for metabolic diseases As a functional food or dietary supplement, used for Prevention and adjuvant treatment of hyperuricemia and gout Especially suitable for early, mild patients or those who are intolerant to drugs such as allopurinol and febuxostat. In the prevention and treatment of diabetes and its complications (such as diabetes nephropathy, neuropathy), its antioxidant and anti-inflammatory effects also show potential.
   • Primary/Secondary Prevention of Cardiovascular Diseases Based on the evidence of improving endothelial function, lowering blood pressure and anti atherosclerosis, it can be used for daily health care of people at high cardiovascular risk.
   • Intervention for neurodegenerative diseases As a nutritional supplement for the nervous system, long-term use may help delay cognitive decline. Further research is needed on its metabolites or the development of delivery systems that can enter the brain.
   • Sports Nutrition and Rehabilitation Its role in reducing oxidative damage, improving muscle blood flow, and mitochondrial function makes it valuable in the fields of exercise nutrition and fatigue recovery.

2. Future research focus and challenges：

   • High quality clinical evidence Currently, most studies are conducted through cell and animal experiments, or small-scale observational studies on populations. It is urgent to conduct large-scale, randomized, double-blind, placebo-controlled clinical trials to confirm its efficacy and optimal dosage for specific diseases.
   • Deep exploration of mechanisms Using omics techniques (proteomics, metabolomics) and systems pharmacology methods, comprehensively map its "compound target pathway disease" network, discover new mechanisms of action and biomarkers.
   • Structural optimization and development of new formulations Through rational chemical modification or advanced delivery technology, overcome the shortcomings of low bioavailability, and develop novel epicatechin derivatives or formulations with clear intellectual property rights.
   • Research on the synergistic effect of multiple components Epicatechins are rarely present alone in natural products. Studying its synergistic effects with other polyphenols (such as anthocyanins, quercetin), vitamins, etc., and developing compound products may result in a "1+1>2" effect.
   • Personalized Nutrition and Medicine Study the impact of genetic polymorphisms (such as differences in metabolic enzymes and transporter genes) on individual epicatechin effects, and promote precise nutritional interventions.

Conclusion

Epicatechins, as a classic natural flavan-3-ol compound, have been extensively studied from their initial antioxidant properties to complex multi-target pharmacological networks and molecular mechanisms. It not only directly scavenges free radicals, but also activates the central regulatory factor NRF2 to activate the body's own antioxidant defense system, thus demonstrating remarkable potential in various aspects such as anti hyperuricemia, anti-inflammatory, cardiovascular and cerebrovascular protection, and neuroprotection. Although it faces challenges such as low bioavailability and rapid metabolism in terms of drug properties, modern pharmaceutical and medicinal chemistry technologies provide feasible solutions for this. In the future, with the continuous deepening of basic research, the continuous accumulation of clinical evidence, and the successful development of new delivery systems, epicatechin is expected to transform from a beneficial dietary component into a functional therapeutic agent with a clear position in the prevention and adjuvant therapy of metabolic diseases, chronic inflammatory diseases, and degenerative diseases. Its research paradigm also provides important references for the development of other multi-target natural products.