Product name: Procyanidin B4
Synonym name: Procyanidol B4；(+)-Catechin-(4α-8)-(-)-epicatechin; (-)-Procyanidin B4
Catalogue No.: BP4256
Cas No.: 29106-51-2
Formula: C₃₀H₂₆O₁₂
Mol Weight: 578.526
Botanical Source:
Type of Compound: Procyanidins

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.

For Reference Standard and R&D, Not for Human Use Directly.

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

Introduction/Overview

Procyanidin B4 (CAS No.: 29106-51-2), an important natural polyphenolic compound, is a dimer member of the procyanidins family. It is formed by the (-)-epicatechin and (+)-catechin units connected by C4→C8 bonds, structurally belonging to hydroxyflavan compounds. In recent years, with the deepening development of natural product pharmacology, proanthocyanidin B4 has attracted widespread attention due to its significant antioxidant, antitumor, and DNA topoisomerase inhibitory activities. Especially in the prevention and treatment of chronic liver diseases such as alcoholic liver injury, proanthocyanidin B4 has shown unique therapeutic potential, making it an important candidate for natural drug development.

This paper will systematically review the chemical structure and physicochemical properties, plant origin, and extraction methods of proanthocyanidin B4, focusing on analyzing its pharmacological activity and mechanism of action. Combined with research progress on related molecular targets, it will comprehensively evaluate its druggability and pharmacokinetic characteristics, and finally discuss its clinical application prospects and future research directions, aiming to provide theoretical basis and practical guidance for the medicinal development of this natural product.

Chemical structure and physicochemical properties

Proanthocyanidin B4 is a dimer formed by two flavan-3-ol units connected by C4 → C8 carbon-carbon bonds, with a specific structure consisting of (-)-epicatechin and (+)-catechin. Its molecular formula is C30H26O12, and its molecular weight is 578.5260. Structurally, proanthocyanidin B4 contains multiple phenolic hydroxyl groups, giving it excellent antioxidant capacity.

In terms of physicochemical properties, proanthocyanidin B4 has a LogP value of 1.7536, indicating moderate lipid solubility and facilitating cell membrane penetration, but low water solubility (0.1369), which to some extent limits its bioavailability. Its topological pole surface area (TPSA) is 220.76 Ų, and higher polarity may affect its transmembrane absorption capacity. The blood-brain barrier penetration ability is relatively low, suggesting limited distribution in the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames-induced mutagenic test result was 0.0, indicating a low genotoxicity risk and a solid safety foundation.

Plant Origins and Extraction Methods

Proanthocyanidin B4 is widely present in various plants, especially those rich in catechin compounds such as grape seeds, cocoa beans, tea, and certain berry plants. Grape seed extract is the main industrial source of proanthocyanidin B4 due to its high content of proanthocyanidins.

The extraction method typically uses organic solvent extraction combined with ultrasound-assisted extraction or microwave-assisted extraction techniques to improve extraction efficiency and purity. Common solvents include ethanol, methanol, and their aqueous solutions. After extraction, separation and identification are performed using liquid chromatography (HPLC) and mass spectrometry (MS) techniques. In recent years, green extraction technologies such as supercritical CO2 extraction and membrane separation have also been applied for efficient extraction of proanthocyanidin B4, balancing environmental friendliness with product quality.

Pharmacological activity research

Antioxidant activity

Due to its multi-hydroxyl structure, proanthocyanidin B4 has a significant free radical scavenging ability, effectively neutralizing reactive oxygen species (ROS) and nitrogen radicals, and reducing cellular damage caused by oxidative stress. In vitro experiments show that proanthocyanidin B4 can significantly increase the activity of superoxide dismutase (SOD1, SOD2) and catalase (CAT), strengthen the cell's antioxidant defense system, and reduce the formation of lipid peroxidation products.

Antitumor effects

Multiple in vitro and in vivo studies have confirmed that proanthocyanidin B4 has inhibitory effects on various tumor cells. Its mechanisms include inducing tumor cell apoptosis, blocking the cell cycle progression, and inhibiting tumor cell migration and invasion. In particular, regarding DNA topoisomerase II (EC 5.99.1.3) inhibition, proanthocyanidin B4 blocks ATP hydrolysis activity, interferes with DNA replication and transcription, and suppresses tumor cell proliferation.

Anti-inflammatory and liver-protective effects

Proanthocyanidin B4 demonstrated good protective effects in alcoholic liver injury models. It suppresses inflammatory responses by regulating inflammatory factors such as tumor necrosis factor (TNF), interleukin-6 (IL6), and interleukin-1β (IL1B). At the same time, it regulates nitric oxide synthase 2 (NOS2) and cytochrome P450 2E1 (CYP2E1) activities, reduces oxidative damage to hepatocytes and lipid peroxidation, and promotes liver function recovery. Additionally, activating the detoxifying enzyme glutathione S-transferase P1 (GSTP1) enhances cellular detoxification ability, further protecting the liver from damage caused by alcohol and its metabolites.

Mechanism of action and molecular targets

The pharmacological effects of proanthocyanidin B4 involve multiple molecular targets and signaling pathways:

1. Antioxidant mechanism: By activating the nuclear factor E2-related factor 2 (Nrf2) signaling pathway, it promotes the expression of antioxidant enzymes (SOD1, SOD2, CAT, NQO1), enhances cellular antioxidant capacity, and reduces cell damage caused by oxidative stress.

2. Anti-inflammatory mechanism: Inhibits the nuclear factor κB (NF-κB) signaling pathway, reduces the expression of pro-inflammatory factors TNF, IL6, IL1B, and NOS2, alleviates inflammatory responses, and protects tissues from inflammatory damage.

3. DNA topoisomerase inhibition: As an inhibitor of DNA topoisomerase II, it blocks ATP hydrolysis activity, interferes with DNA replication and repair processes, induces tumor cell apoptosis, and exerts anti-tumor effects.

4. Detoxification and metabolic regulation: Regulates CYP2E1 activity, reduces the production of harmful free radicals in alcohol metabolism, activates GSTP1 to promote metabolic elimination of harmful substances, and synergistically protects liver cells.

In summary, proanthocyanidin B4 exerts its broad biological effects through multi-target and multi-pathway synergistic effects.

Druggability evaluation and pharmacokinetics

From the perspective of druggability, proanthocyanidin B4 has the following characteristics:

• Moderate molecular weight, which is beneficial for drug design and modification.
• The LogP value is moderate (1.75), with some lipophilic and water-soluble properties, which facilitates cell membrane penetration.
• TPSA was relatively high (220.76 Ų), indicating greater polarity, which may affect oral absorption and bioavailability.
• Water solubility is relatively low (0.1369), limiting its distribution and absorption in the body, requiring formulation improvements to improve solubility.
• It has low blood-brain barrier penetration ability, making it suitable for peripheral target diseases and reducing the risk of central nervous system side effects.
• No hERG channel inhibition or genotoxicity, with good safety.

Pharmacokinetics, existing studies show that proanthocyanidin B4 is absorbed orally with limited absorption and low bioavailability, mainly affecting blood drug concentrations through intestinal metabolism and hepatic first-pass effects. Its metabolites include various phenolic acids and small-molecule flavanols, which have certain biological activity. In the future, new delivery systems such as nanocarriers and liposomes will need to improve their pharmacokinetic performance.

Prospects and outlooks for clinical applications

Proanthocyanidin B4, as a natural polyphenolic compound, exhibits multi-target and multi-mechanism pharmacological activity, showing promising application prospects especially in antioxidant, anti-inflammatory, and liver protection fields. Its protective effect in alcoholic liver injury offers new ideas for adjunctive treatment of chronic liver disease. In addition, its antitumor activity also lays the foundation for its development in the field of adjuvant therapy on tumors.

However, the clinical translation of proanthocyanidin B4 still faces many challenges, including low bioavailability, insufficient in vivo stability, and weak targeting. Future research should focus on:

• Optimized extraction and purification processes to obtain high-purity, highly active proanthocyanidin B4;
• Enhancing bioavailability and in vivo stability through chemical modification and novel delivery systems;
• In-depth analysis of its molecular mechanisms to uncover more potential targets;
• Conduct systematic pharmacokinetic and toxicological evaluations to ensure safety;
• Design reasonable clinical trials to verify efficacy and safety.

In addition, by combining modern omics technology with computational pharmacology, the development of precision drugs for proanthocyanidin B4 will greatly advance its clinical application.

Conclusion

Proanthocyanidin B4, a naturally characterized and biologically active natural product, demonstrates broad medicinal value due to its antioxidant, anti-tumor, and hepatoprotective effects. Through systematic chemical, pharmacological, and drug-making studies, proanthocyanidin B4 is expected to become an important candidate molecule for developing novel natural drugs. In the future, it is necessary to enhance pharmacokinetic optimization and clinical validation, promote its transition from laboratory to clinical application, and provide new natural drug solutions for the prevention and treatment of related diseases.