Product name: Glicoricone
Synonym name:
Catalogue No.: BP4665
Cas No.: 161099-37-2
Formula: C₂₁H₂₀O₆
Mol Weight: 368.385
Botanical Source:
Type of Compound: Flavonoids

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

Licorice (Glycyrrhiza spp.), as a traditional Chinese medicinal material, has long attracted significant attention in scientific research and clinical practice due to its diverse pharmacological activities and abundant natural product components. Glycoricone (CAS No.: 161099-37-2) is a phenolic natural compound isolated from licorice root. In recent years, it has become a hot topic in pharmacological research due to its unique biological activity. Glycyrrhizone not only exhibits monoamine oxidase (MAO) inhibitory activity but also has estrogen receptor (ER) antagonism, indicating potential multi-target pharmacological effects. Especially in the anti-ulcer field, glycyrrhizone exerts significant protective effects by modulating multiple related targets, suggesting its potential application in the treatment of gastrointestinal diseases.

This paper aims to systematically review the chemical structure and physicochemical properties, plant origin, and extraction methods of glycyrrhizone, deeply analyze its pharmacological activity and mechanism of action, evaluate its druggability parameters and pharmacokinetic characteristics, and explore its clinical application prospects and future research directions, providing theoretical basis and reference for the drug development and clinical translation of glycyrrhizone.

Chemical structure and physicochemical properties

Glycyrrhizone is a phenolic compound with a molecular formula of C21H20O6 and a molecular weight of 368.3850. Its chemical structure contains multiple hydroxyl and phenol hydroxyl groups, giving it strong polarity and biological activity. The LogP value of glycyrrhizone is 3.4405, indicating moderate lipid solubility, which facilitates cell membrane penetration and distribution in vivo. The polar surface area (TPSA) is 100.1300, indicating that its molecules have certain polar characteristics that facilitate binding to biological macromolecules such as enzymes and receptors.

Low water solubility (0.0892 mg/mL) limits its solubility in the aqueous phase and may affect oral bioavailability. The blood-brain barrier has relatively low permeability, suggesting limited distribution in the central nervous system, which may reduce central side effects. The hERG channel inhibition test was negative, indicating that glycyrrhizone carries a lower risk of cardiotoxicity. The Ames-induced mutagenic test scored 0.6, indicating a low genotoxicity risk and meeting preliminary safety requirements.

In summary, glycyrrhizone has moderate physicochemical properties and certain drug development potential, but its water solubility and bioavailability still need optimization.

Plant Origins and Extraction Methods

Licyrrhizone mainly comes from the roots of licorice plants, which are widely distributed in Asia, Europe, and North America. Licorice root contains various active ingredients, including glycyrrhizic acid, licorice flavonoids, and various phenolic compounds, among which glycyrrhizone is one of them.

Common methods for extracting glycyrrhizone include solvent extraction, column chromatography separation, and high-performance liquid chromatography (HPLC) purification. First, ethanol or methanol is used for reflux extraction of dried licorice roots. After concentration, the extract is separated by silica gel column chromatography. Combined with gradient elution technology, glycyrrhizone can be effectively isolated. Purification and quantitative analysis are further performed using reversed-phase HPLC to ensure the purity and quality of the extracts.

In recent years, ultrasound-assisted extraction and microwave-assisted extraction technologies have also been applied to glycyrrhizone extraction, significantly improving extraction efficiency and yield. In addition, the use of green solvents such as ethyl acetate and ethanol aligns with the modern concept of environmentally friendly extraction from natural products.

Pharmacological activity research

Monoamine oxidase (MAO) inhibitory activity

Glycyrrhizone exhibits an inhibitory effect on monoamine oxidase, with an IC50 of about 140 μM. Monoamine oxidase, as a key enzyme in neurotransmitter metabolism, is involved in the pathological processes of various neuropsychiatric diseases. Glycyrrhizone may regulate brain monoamine neurotransmitter levels by inhibiting MAO activity, offering potential antidepressant and neuroprotective effects. Although its MAO inhibitory activity is moderate, combined with its low blood-brain barrier permeability, it suggests that its effects may be more manifested in peripheral or local tissues.

Estrogen receptor (ER) antagonism

Glycyrrhizone can bind to estrogen receptors and exhibits estrogen antagonist activity. This characteristic gives it potential application value in hormone-related diseases such as breast cancer and endometriosis. By blocking the ER signaling pathway, glycyrrhizone may inhibit the proliferation of estrogen-dependent cells, exerting antitumor effects.

Anti-ulcer activity

Glycyrrhizone has shown significant protective effects in ulcer research. Its targets cover a variety of gastrointestinal-related molecules, including:

• PTGS1 (COX-1) and PTGS2 (COX-2): Glycyrrhizone regulates prostaglandin synthesis, promotes gastric mucosal protection, and reduces gastric acid-related damage.
• MUC5AC: Promotes gastric mucus secretion and strengthens the gastric mucosal barrier function.
• GAST (gastrin) and CCKBR (cholecystokinin B receptor): regulate gastric acid secretion and maintain a stable stomach environment.
• SST (Somatostatin) and HRH2 (Histamine H2 receptor): Involved in negative feedback regulation of gastric acid secretion.
• H+/K+-ATPase: Directly inhibits proton pumps, reduces gastric acid secretion, and relieves gastric mucosal damage.
• TGFα (Transforming Growth Factor α): Promotes repair and regeneration of the gastric mucosa.

Through multi-target coordinated regulation, glycyrrhizone effectively alleviates the pathological progression of gastric ulcers and related gastrointestinal diseases.

Mechanism of action and molecular targets

The pharmacological effects of glycyrrhizone involve multiple signaling pathways and multiple molecular targets, reflecting its multi-target and multi-mechanism characteristics.

Monoamine oxidase inhibition mechanism

Glycyrrhizone binds to the active site of MAO enzymes, inhibiting its catalytic activity of monoamine neurotransmitter oxidation, prolonging the duration of neurotransmitter action in the synaptic cleft, and regulating nervous system function. Although its inhibitory effect is not as strong as that of classic MAO inhibitors, combined with low blood-brain barrier permeability, it may exert regulatory effects in the peripheral nervous system or other tissues.

Estrogen receptor antagonism mechanism

After glycyrrhizone binds to ER, it blocks the transcriptional activity activated by estrogen, suppresses the expression of estrogen-dependent genes, and thereby suppresses cell proliferation and promotes apoptosis. This mechanism provides a theoretical basis for the potential application of glycyrrhizone in the treatment of hormone-related tumors.

Anti-ulcer mechanism

Glycyrrhizone regulates the gastrointestinal environment through multiple targets:

• Inhibits PTGS1 and PTGS2, regulates prostaglandin synthesis, and enhances gastric mucosal defense.
• Promotes MUC5AC expression and increases mucus protective layer thickness.
• Regulates GAST and CCKBR to reduce excessive gastric acid secretion.
• It acts on SST and HRH2, regulating neuroendocrine feedback for gastric acid secretion.
• Inhibits H+/K+-ATPase activity, directly reducing gastric acid secretion.
• Promotes TGFα expression and aids gastric mucosal repair.

These functions together maintain the integrity of the gastric mucosa and prevent and repair ulcer lesions.

Druggability evaluation and pharmacokinetics

The druggability parameters of glycyrrhizone indicate that it has certain potential for drug development:

• The molecular weight (368.3850) complies with the Lipinski rule, facilitating oral absorption.
• LogP (3.4405) is moderate, balancing lipid solubility and water solubility, which is beneficial for membrane permeability.
• TPSA (100.1300) indicates moderate polarity, which is beneficial for target binding.
• Water solubility (0.0892) is relatively low, which may limit oral bioavailability and requires improvement through formulation technology.
• The blood-brain barrier has low permeability, reducing the risk of central nervous system side effects.
• hERG inhibitor is negative, with a low risk of cardiotoxicity.
• The Ames test has low mutagenicity and good safety.

Currently, pharmacokinetic studies of glycyrrhizone are limited. Preliminary data indicate that its oral absorption rate is moderate, metabolism mainly occurs through hepatic enzyme systems, and its half-life is moderate. In the future, further systematic pharmacokinetic and toxicological studies are needed to clarify its in vivo behavior and safety.

Prospects and outlooks for clinical applications

With its multi-target pharmacological activity, especially its potential in ulcer and hormone-related diseases, glycyrrhizone has promising clinical application prospects.

• Anti-ulcer drug development: Glycyrrhizone regulates gastric acid secretion and protects the gastric mucosa through multiple targets, making it a potential candidate for new anti-ulcer drugs. Combining traditional medicinal experience with licorice to develop safe and effective oral formulations is of great significance.
• Adjunctive therapy for neuropsychiatric disorders: MAO's inhibitory activity suggests its potential application in depression and neurodegenerative diseases, especially suitable for adjunctive treatment of peripheral nervous system diseases.
• Hormone-related tumor therapy: ER antagonistic activity offers a new approach for glycyrrhizone in treating estrogen-dependent tumors such as breast cancer, and is expected to be developed as a naturally derived antisteroid drug.

Future research should focus on:

• Optimizing the formulation of glycyrrhizone to improve its water solubility and bioavailability.
• Systematically conduct pharmacokinetic and toxicological studies to ensure clinical safety.
• Through structural modification and pharmacodynamic optimization, its MAO inhibitory and ER antagonistic activities are enhanced.
• Conduct preclinical animal models and clinical trials to verify efficacy and safety.

Conclusion

As an important phenolic active component in licorice, glycyrrhizone demonstrates unique multi-target pharmacological activity, especially showing great potential in the fields of ulcer and hormone-related diseases. Its reasonable physicochemical properties and good safety lay the foundation for drug development. In the future, through in-depth mechanistic research, drug design optimization, and clinical validation, glycyrrhizone is expected to become an innovative class of natural product drugs, offering new options for the treatment of related diseases. The ongoing development of natural product pharmacology will drive the application of glycyrrhizone and its derivatives in modern medicine to new heights.