Licochalcone A
[CAS# 58749-22-7]

Identification

• Classification: Biochemical >> Plant extracts
• Name: Licochalcone A
• Synonyms: (E)-3-[4-hydroxy-2-methoxy-5-(2-methylbut-3-en-2-yl)phenyl]-1-(4-hydroxyphenyl)prop-2-en-1-one
• Molecular Formula: C₂₁H₂₂O₄
• Molecular Weight: 338.40
• CAS Registry Number: 58749-22-7
• EC Number: 635-678-2
• SMILES: CC(C)(C=C)C1=C(C=C(C(=C1)/C=C/C(=O)C2=CC=C(C=C2)O)OC)O

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 532.6±50.0 °C 760 mmHg (Calc.)^*
• Flash point: 186.9±23.6 °C (Calc.)^*
• Index of refraction: 1.611 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302+H312+H332-H302-H312-H332
• Safety Statements: P261-P264-P270-P271-P280-P301+P317-P302+P352-P304+P340-P317-P321-P330-P362+P364-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319

Discovery and Applications

Licochalcone A is a naturally occurring chalcone, a type of flavonoid, primarily isolated from the roots and rhizomes of Glycyrrhiza species, particularly Glycyrrhiza inflata. Structurally, it is characterized by an open-chain flavonoid backbone with two aromatic rings connected by a three-carbon α,β-unsaturated carbonyl system, which contributes to its diverse biological activities. Licochalcone A has attracted considerable interest due to its pharmacological properties, including anti-inflammatory, antioxidant, antimicrobial, anticancer, and hepatoprotective effects.

The discovery of licochalcone A originated from phytochemical investigations of licorice plants, traditionally used in Chinese and Ayurvedic medicine for the treatment of respiratory, gastrointestinal, and liver disorders. Through extraction, chromatography, and spectroscopic techniques, licochalcone A was isolated and structurally elucidated, enabling studies into its mechanisms of action and therapeutic potential.

Pharmacologically, licochalcone A exhibits strong anti-inflammatory activity. It can inhibit the expression of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukins, and suppress enzymes involved in inflammation, including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). These effects are mediated through modulation of signaling pathways such as NF-κB and MAPK, which regulate inflammation and cellular stress responses. Such properties make licochalcone A a promising candidate for managing chronic inflammatory diseases.

Licochalcone A also demonstrates significant antioxidant activity. Its phenolic hydroxyl groups enable it to scavenge reactive oxygen species (ROS) and reduce oxidative stress, thereby protecting cells from lipid peroxidation and DNA damage. This antioxidant capacity contributes to its hepatoprotective effects and potential applications in preventing oxidative stress–related disorders.

The compound exhibits antimicrobial activity against a wide range of bacteria, fungi, and parasites. It can disrupt microbial cell membranes, inhibit biofilm formation, and interfere with enzymatic pathways essential for microbial survival, supporting its use as a natural antimicrobial agent. Additionally, licochalcone A has demonstrated anticancer activity in various in vitro and in vivo studies by inducing apoptosis, cell cycle arrest, and inhibition of tumor cell proliferation across multiple cancer types, including breast, liver, and colon cancers.

Licochalcone A also shows hepatoprotective and neuroprotective effects. In hepatocytes, it can attenuate oxidative stress and inflammation, reducing liver injury caused by toxins or disease conditions. In neuronal cells, it modulates signaling pathways involved in cell survival, neuroinflammation, and apoptosis, indicating potential applications in neurodegenerative diseases.

Despite its promising pharmacological activities, licochalcone A has limited water solubility, which restricts its bioavailability. Researchers are investigating various formulation strategies, including nanoparticles, liposomes, and cyclodextrin inclusion complexes, to improve solubility, stability, and systemic absorption, enhancing its therapeutic efficacy.

Overall, licochalcone A is a bioactive chalcone with diverse pharmacological properties, including anti-inflammatory, antioxidant, antimicrobial, anticancer, hepatoprotective, and neuroprotective effects. Its historical use in traditional medicine, combined with contemporary research on its mechanisms and applications, highlights its potential as a therapeutic agent across multiple disease areas.

References

2024. Licochalcone A decreases cancer cell proliferation and enhances ferroptosis in acute myeloid leukemia through suppressing the IGF2BP3/MDM2 cascade. Annals of Hematology, 103(9).
DOI: 10.1007/s00277-024-06003-4

2024. Licochalcone A Ameliorates Aspergillus fumigatus Keratitis by Reducing Fungal Load and Activating the Nrf2/HO-1 Signaling Pathway. ACS Infectious Diseases, 10(9).
DOI: 10.1021/acsinfecdis.4c00123

2025. Licochalcone A Ameliorates Cognitive Dysfunction in an Alzheimer’s Disease Model by Inhibiting Endoplasmic Reticulum Stress-Mediated Apoptosis. Journal of Geriatric Psychiatry and Neurology, 38(5).
DOI: 10.1177/08919887241295730