Synonym name: Cacticin
Catalogue No.: BP0797
Cas No.: 6743-92-6
Formula: C₂₂H₂₂O₁₂
Mol Weight: 478.406
Botanical Source: Found in Cereus grandiflorus and others

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.

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

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

Introduction/Overview

Isorhamnetin 3-O-galactoside (CAS No.: 6743-92-6) is an important flavonoid glycoside derivative, widely found in various plants, especially abundant in the celery genus Oenanthe javanica. As the glycoside form of isorhamin, this compound not only retains the typical biological activity of flavonoids but also exhibits unique pharmacological properties due to glycoside modification. In recent years, isorhamin-3-O-galactoside has become one of the hot natural products in research on thrombotic diseases and related liver injury due to its remarkable antithrombotic and fibrinolytic activity. This paper systematically reviews the chemical structure, physicochemical properties, plant origin, and extraction method of isorhamnumin 3-O-galactoside, focusing on its pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects, aiming to provide a theoretical foundation and reference for subsequent drug development and clinical application.

Chemical structure and physicochemical properties

Isorhamnoside 3-O-galactoside belongs to the flavonoid glycoside class, with a molecular formula of C_22H_22O_12 and a molecular weight of 478.4060. Its structure is formed by isorhaminin (3'-methoxyflavones) as the aglycon, connected to galactoside glycosides at the 3-hydroxyl position. This structure imparts its typical flavonoid backbone features, including two aromatic rings (A and B rings) and one oxygen heterocycle (C ring), as well as substitutions of methoxy and hydroxyl groups, enhancing its bioactivity and water solubility.

In terms of physicochemical properties, the LogP value of isorhamnum 3-O-galactoside is about -0.0055, indicating strong hydrophilicity, with a water solubility of 1.8289, matching the water-solubility characteristics of flavonoid glycosides. Its topological pole surface area (TPSA) is 199.5100, indicating a relatively high polar surface area indicating weaker ability to pass through cell membranes and low blood-brain barrier penetration. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames mutagenicity test score was 0.6, indicating that the compound has a low genotoxicity risk and a solid safety foundation.

Plant Origins and Extraction Methods

Isorhamnosin 3-O-galactoside is mainly isolated from water celery (Oenanthe javanica). Water celery is an aquatic or wetland plant widely distributed in Asia, commonly used in traditional Chinese medicine for clearing heat and detoxifying, promoting urination, and reducing swelling. Plants are rich in various flavonoids and their glycosides, with isorhamnum 3-O-galactoside being relatively high.

The extraction method typically uses alcohol extraction combined with chromatography separation technology. The specific steps include:

1. Raw material preparation: collect fresh or dried above-ground celery, crush it for later use.
2. Solvent extraction: Use 70%-80% ethanol or methanol for reflux or ultrasound-assisted extraction to improve the leaching rate of flavonoid glycoside components.
3. Concentration and separation: After concentration under reduced pressure, the filtrate is extracted by liquid-liquid extraction to remove fat-soluble impurities.
4. Chromatographic purification: Further purification by silica gel column chromatography, reversed-phase C18 column chromatography, or high-performance liquid chromatography (HPLC) yields high-purity isoishamhamin 3-O-galactoside.

In recent years, the introduction of supercritical CO_2 extraction and membrane separation technologies has provided new ideas for efficient extraction of isorhamnumin 3-O-galactoside, improving extraction efficiency and purity.

Pharmacological activity research

Research on the pharmacological activity of isorhamnumin 3-O-galactoside mainly focuses on antithrombotic, fibrinolytic, and hepatoprotective effects. In addition, its antioxidant and anti-inflammatory activities are also receiving increasing attention.

Antithrombotic and fibrinolytic activity

Thrombosis is the pathological basis of various cardiovascular and cerebrovascular diseases. Regulating thrombin and factor Xa activity is a key target for antithrombotic therapy. Isorhamnin 3-O-galactoside can significantly inhibit thrombin and factor Xa (FXa) activity, reducing the maximum rate of thrombin-catalyzed fibrin polymerization, thereby inhibiting thrombosis. Its mechanism also includes inhibiting FXa production and FVa/FXa-mediated thrombin production, weakening the coagulation cascade.

Additionally, this compound can inhibit the secretion of plasminogen activator inhibitor-1 (PAI-1) induced by tumor necrosis factor-α (TNF-α), reduce the PAI-1/tissue-type plasminogen activator (t-PA) ratio, promote fibrinolytic activity, improve hemorheological status, and further exert antithrombotic effects.

Hepatoprotective effects

Isorhamnin 3-O-galactosinoside demonstrated significant protective effects in liver injury models. Using carbon tetrachloride (CCl_4) induced liver injury in mice as a model, studies have shown that this compound can reduce hepatocyte necrosis, lower serum transaminase levels, inhibit inflammatory responses and oxidative stress, and promote liver tissue repair. Its hepatoprotective effect is closely related to antioxidant capacity, regulating redox balance, reducing the generation of reactive oxygen species (ROS), and alleviating oxidative damage.

Antioxidant and anti-inflammatory activities

Isorhamnosin 3-O-galactoside activates the NFE2L2/NRF2 signaling pathway, upregulating the expression of antioxidant enzymes such as superoxide dismutase (SOD1, SOD2), catalase (CAT), glutathione peroxidase (GPX1), and heme oxygenase-1 (HMOX1), thereby enhancing the body's antioxidant defense capacity and reducing oxidative stress-mediated cell damage.

At the same time, this compound can inhibit the expression of inflammatory factors, reduce the release of pro-inflammatory cytokines such as TNF-α and IL-6, regulate immune responses, and exert anti-inflammatory effects.

Mechanism of action and molecular targets

The mechanism of action of isorhamnumin 3-O-galactosinoside involves multiple signaling pathways and key molecular targets, mainly including:

1. Thrombin and factor Xa inhibition
   By directly inhibiting the enzyme activity of thrombin and factor Xa, it blocks the coagulation cascade, reduces fibrin formation, and prevents thrombosis.

2. Regulates the fibrinolytic system
   Inhibits PAI-1 secretion induced by TNF-α, reduces the PAI-1/t-PA ratio, promotes fibrinolysin activity, and promotes thrombolysis.

3. Activation of antioxidant signaling pathways
   Activates NFE2L2/NRF2 transcription factors, promotes the expression of antioxidant enzyme genes, removes excess reactive oxygen species, and protects cells from oxidative damage.

4. Anti-inflammatory effects
   Inhibits the expression of pro-inflammatory cytokines TNF-α and IL-6, reduces inflammatory responses, and protects tissue structure.

5. Liver protection mechanisms
   Through multi-target synergistic action, it alleviates CCl_4-induced hepatocyte injury and promotes hepatocyte repair and regeneration.

In summary, isorhamnin 3-O-galactoside regulates blood coagulation, fibrinolysis, oxidative stress, and inflammatory responses through multiple targets and pathways, demonstrating promising therapeutic potential.

Druggability evaluation and pharmacokinetics

The druggability evaluation of isorhamnumin 3-O-galactoside shows it has a solid foundation for safety and pharmacological activity:

• Molecular weight and polarity: molecular weight 478.4, TPSA 199.5, indicating high polarity and good water solubility, but may limit cell membrane permeability and oral bioavailability.
• Lipid solubility: LogP is close to zero, indicating a balance of hydrophilicity and hydrophobicity, suitable for distribution in the body.
• Blood-brain barrier permeability: Predicted as low, indicating limited role in the central nervous system, suitable for treating peripheral vascular-related diseases.
• Cardiotoxicity: No hERG channel inhibition, reducing the risk of arrhythmias.
• Genotoxicity: The Ames test has low mutagenicity and relatively high safety.

In terms of pharmacokinetics, current research is relatively limited. Due to its good water solubility, oral absorption may be limited by the hydrolysis and metabolism of glycoside structures. In the future, further in vivo pharmacokinetic studies are needed to clarify its absorption, distribution, metabolism, and excretion characteristics, and optimize administration regimens.

Prospects and outlooks for clinical applications

Isorhamnin 3-O-galactosinoside demonstrates broad clinical application prospects due to its multiple pharmacological activities such as antithrombotic, fibrinolytic, and hepatoprotective effects:

1. Thrombotic vascular disease
   It inhibits thrombin and factor Xa activity, regulates the fibrinolytic system, and is suitable for adjunctive treatment or prevention of thrombosis-related diseases such as arteriosclerosis, venous thrombosis, and pulmonary embolism.

2. Liver damage and liver diseases
   It has protective effects against CCl_4-induced liver injury, and future research may expand to treatment of drug-induced liver injury, alcoholic liver disease, and non-alcoholic steatohepatitis.

3. Antioxidant and anti-inflammatory diseases
   By activating the NRF2 signaling pathway, it alleviates oxidative stress and inflammatory responses, potentially offering adjunctive therapeutic value for cardiovascular diseases, metabolic syndrome, and chronic inflammatory diseases.

However, the clinical translation of isorhamnum 3-O-galactosinoside still faces many challenges, including in vivo stability, oral bioavailability, formulation development, and systematic safety evaluation. In the future, research on pharmacokinetics, toxicology, and preclinical trials should be strengthened to explore the potential of combination therapy and precise delivery strategies.

Conclusion

Isorhamnum 3-O-galactosinoside, a natural flavonoid glycoside derived from Oenanthe javanica, demonstrates promising application potential in antithrombotic properties, fibrinolysis promotion, and liver protection due to its unique chemical structure and multi-target pharmacological activity. By inhibiting key coagulation factors, regulating the fibrinolytic system, activating antioxidant signaling pathways, and suppressing inflammatory responses, it exerts multidimensional biological effects. Druggability evaluations indicate good safety, but pharmacokinetic characteristics still require further study. In the future, leveraging modern drug development technologies, isorhamnin 3-O-galactoside is expected to become a novel natural drug candidate for treating thrombotic diseases and liver injury-related conditions. Systematic pharmacological mechanism elucidation and preclinical research will lay a solid foundation for its clinical translation, promoting its in-depth development in the field of natural product pharmacology.