Product name: Agrimoniin
Synonym name:
Catalogue No.: BP4708
Cas No.: 82203-01-8
Formula: C₈₂H₅₄O₅₂
Mol Weight: 1871.28
Botanical Source:
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.

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

Agrimoniin, CAS number 82203-01-8, is a typical dimeric hydrolyzable tannin, mainly found in the traditional Chinese medicinal herb Agrimonia pilosa Ledeb. As a natural polyphenolic compound, Agrimonia has attracted widespread attention in the field of natural product pharmacology in recent years due to its unique chemical structure and diverse biological activities. Its antitumor activity and ability to regulate the immune factor interleukin-1 suggest its potential application value in tumor treatment and immune regulation. In addition, the role of aggregation in hemostasis mechanisms and its interactions with various coagulation factors and plasma proteins provide new ideas for clinical development.

This paper aims to systematically review the chemical structure and physicochemical properties of aggregatorium, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics. Combined with its clinical application prospects, it comprehensively assesses its potential as a natural drug candidate molecule to promote its in-depth development in basic research and clinical translation.

Chemical structure and physicochemical properties

Agrimonia is a dimeric hydrolyzable tannin with a molecular weight as high as 1871.2820, and a complex structure. Its molecule is formed by two ellagitannin monomers bridged by a dehydrohexahydroxydiphenoyl (DHHDP) group. This structure imparts abundant phenolic hydroxyl groups, resulting in extremely high polarity and a large topological pole surface area (TPSA of 877.36 Ų), which also explains its extremely low water solubility (about 0.0001 mg/mL) and low lipid solubility (LogP about 2.56).

The chemical backbone of aggregation includes multiple phenolic hydroxyl and ester bonds, making it easy to hydrolyze and is a typical hydrolyzed tannin. Its complex polyphenol structure gives it strong antioxidant capacity, but also limits its metabolism and bioavailability in the body. Due to its high molecular weight and polarity, aggregated trivia has difficulty crossing the blood-brain barrier (low BBB permeability), and in vitro hERG channel inhibition tests showed no significant cardiotoxicity risk. Ames mutagenic test results were 0.6, indicating low genotoxicity risk and good safety.

Plant Origins and Extraction Methods

Agrimonia pilosa Ledeb. is mainly found in the Agrimonia pilosa Ledeb. genus, especially in its above-ground parts (stems and leaves). In traditional Chinese medicine, cinquefer is widely used in fields such as hemostasis, anti-inflammation, antibacterial, and anti-tumor properties. Its pharmacological activity is partly attributed to its abundant polyphenolic compounds, especially aggremes.

Common methods for extracting aggregatorium include:

1. Solvent extraction: Using ethanol-water mixed solvents (such as 70% ethanol) for reflux extraction, combined with ultrasound-assisted extraction technology, improves extraction efficiency.
2. Liquid-liquid distribution: The crude extract is distributed through ethyl acetate or n-butanol to remove fat-soluble impurities and enrich water-soluble polyphenols.
3. Column chromatography separation: Separation and purification are performed using polyamide columns, C18 reversed-phase columns, or Sephadex LH-20 columns, combined with gradient elution to obtain high-purity aggregatoryl.
4. High-Performance Liquid Chromatography (HPLC): Used for component analysis and purity detection, often used in conjunction with mass spectrometry (LC-MS) to identify structures.

In recent years, supercritical fluid extraction and membrane separation technologies have also been attempted for the extraction and purification of aggregatorium, aiming to improve yield and environmental friendliness.

Pharmacological activity research

The pharmacological effects of aggregatorin cover multiple aspects, including anti-tumor, anti-inflammatory, immunomodulatory, and hemostasis.

Antitumor activity

Numerous in vitro cell experiments and animal model studies have shown that aggregatorin has significant antitumor activity. Its main mechanisms include:

• Induction of tumor cell apoptosis: By activating mitochondrial pathways, it regulates the expression of Bcl-2 family proteins, promoting programmed cell death.
• Inhibition of tumor cell proliferation: Blocks cell cycle progression, especially during G0/G1 phase stagnation.
• Anti-angiogenesis: Inhibits the expression of vascular endothelial growth factor (VEGF) in the tumor microenvironment, limiting tumor angiogenesis.
• Regulates the immune microenvironment: Promotes the expression of inflammatory factors such as interleukin-1 (IL-1), activates the body's immune response, and enhances anti-tumor immune effects.

Anti-inflammatory and immunomodulatory

Agrimonia can regulate various inflammatory mediators and signaling pathways, exerting anti-inflammatory effects. Its ability to induce interleukin-1 suggests its important role in immune regulation, possibly enhancing the body's defense by activating macrophages and other immune cells.

Hemostatic effect

Research on aggregation in the field of hemostasis is relatively novel. It regulates coagulation cascades and promotes hemostasis by interacting with various coagulation factors (such as F2, F7, F9, F10) and plasma proteins (such as plasma protein C, PROC, and VWF). Its regulatory effect on SERPINE1 (plasma plasminogen activator inhibitor 1) further affects the fibrinolytic system and maintains the balance between hemostasis and fibrinolysis.

Mechanism of action and molecular targets

The multi-target mechanism of aggregated hormone is the foundation of its multiple pharmacological effects.

Antitumor mechanism

• Mitochondrial pathway activation: Agrimonin promotes mitochondrial membrane potential loss by regulating the Bax/Bcl-2 ratio, releasing cytochrome c, activating the caspase cascade, and inducing tumor cell apoptosis.
• Signaling pathway regulation: Inhibits PI3K/Akt and NF-κB signaling pathways, reducing tumor cell proliferation and invasion capacity.
• Immune factor induction: Induces IL-1 and other pro-inflammatory cytokines, activates immune cells, and enhances anti-tumor immune surveillance.

Hemostasis-related targets

Agrimonia regulates the hemostasis process through multiple targets:

• Coagulation factor activation: Enhances the activity of thrombin (F2) and coagulation factors F7, F9, and F10, accelerating the coagulation cascade.
• VWF effect: promotes the interaction between platelets and vascular endothelium, enhancing platelet aggregation.
• Regulation of the protein C system: Affects the activity of anticoagulant protein C (PROC), maintaining coagulation and anticoagulation balance.
• Fibrinolytic system regulation: modulates SERPINE1 expression, inhibits plasminogen activation, reduces thrombolysis, and promotes hemostasis.

These effects together promote rapid hemostasis, reduce bleeding time, and have potential clinical value.

Druggability evaluation and pharmacokinetics

The druggability evaluation of Agrimonia Extract shows that it presents certain challenges:

• Molecular weight and polarity: High molecular weight (1871 Da) and extremely high TPSA (877.36 Ų) limit its oral absorption and cell membrane penetration capabilities.
• Extremely low water solubility: water solubility is only 0.0001 mg/mL, limiting its bioavailability.
• Low blood-brain barrier penetration: difficult to enter the central nervous system, suitable for peripheral targeted therapy.
• Good safety: No significant hERG channel inhibition, Ames test results show low risk of mutagenic inducement, and relatively high safety.

Currently, pharmacokinetic studies on aggregation are limited. Preliminary data indicate that its oral absorption rate is low, and its metabolism in the body mainly occurs through degradation of intestinal microbes and liver metabolism, with metabolites possibly having certain biological activity. In the future, further in vivo pharmacokinetics and metabolic kinetics research is needed to optimize delivery routes and dosage form design.

Prospects and outlooks for clinical applications

As a natural polyphenol drug candidate molecule, Agrimonia Extract possesses multi-target and multi-pathway pharmacological activity, demonstrating broad clinical application potential.

• Antitumor drug development: Their induction of tumor cell apoptosis and immunomodulatory effects offer new ideas for adjuvant therapy on tumors. By combining nanocarrier technology or structural modification to enhance bioavailability, it is expected to be developed into new anti-tumor drugs.
• Hemostatic Agent Applications: For surgical bleeding, trauma hemostasis, and blood disorders, Agrimonium has the potential to act as a natural hemostatic agent by regulating coagulation factors and the fibrinolytic system.
• Immunomodulators: Induce interleukin-1 and regulate immune cell function, potentially used in the treatment of immunodeficiency and inflammatory diseases.
• Multifunctional compound preparations: combine other drug ingredients to exert synergistic effects and expand their clinical indications.

Future research should focus on:

1. Structural optimization and derivatives design: Improving pharmacokinetic properties, enhancing oral absorption and targeting.
2. Formulation innovation: developing nanoformulations, liposomes, or sustained-release systems to enhance in vivo stability and targeted delivery.
3. Systematic pharmacology and network pharmacology research: In-depth analysis of its multi-target action network to guide precision treatment.
4. Preclinical and clinical trials: Verify their safety and efficacy, driving clinical translation.

Conclusion

As a typical dimeric hydrolyzed tannin, aggregated ketan demonstrates significant anti-tumor, hemostatic, and immunomodulatory potential due to its complex chemical structure and diverse biological activities. Although its high molecular weight and polarity pose certain druggability challenges, modern drug development technologies may help overcome these limitations and achieve clinical application. In the future, combining systemic pharmacology, pharmacokinetics, and clinical research, aggrebulin is expected to become an important candidate molecule for natural product drug development, providing new therapeutic strategies for tumor treatment and hemostasis management.