Isoliquiritigenin
[CAS# 961-29-5]

Identification

• Classification: Biochemical >> Natural biochemical product
• Name: Isoliquiritigenin
• Synonyms: (E)-1-(2,4-Dihydroxyphenyl)-3-(4-hydroxyphenyl)-2-propen-1-one; 4,2',4'-Trihydroxychalcone
• Molecular Formula: C₁₅H₁₂O₄
• Molecular Weight: 256.25
• CAS Registry Number: 961-29-5
• EC Number: 677-489-8
• SMILES: C1=CC(=CC=C1/C=C/C(=O)C2=C(C=C(C=C2)O)O)O

Properties

• Solubility: 20 mg/mL (DMSO), <0.1 mg/mL (water) (Expl.)
• Density: 1.4±0.1 g/cm³, Calc.^*
• Melting point: 185-187 °C (Expl.)
• Index of Refraction: 1.715, Calc.^*
• Boiling Point: 504.0±42.0 °C (760 mmHg), Calc.^*
• Flash Point: 272.7±24.4 °C, Calc.^*

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315

Discovery and Applications

Isoliquiritigenin (C15H12O4) is a naturally occurring flavonoid compound found in various plants, notably in the roots of Glycyrrhiza glabra (licorice). It belongs to the chalcone class of flavonoids and is characterized by its distinctive chemical structure, which includes a phenyl group and a carbonyl group attached to a conjugated double bond system. The compound has attracted attention due to its diverse range of biological activities and potential health benefits. Isoliquiritigenin is often studied for its antioxidant, anti-inflammatory, anticancer, and neuroprotective properties, and its applications span both traditional and modern therapeutic uses.

The discovery of isoliquiritigenin can be traced back to the early studies of the chemical constituents of licorice, where researchers isolated and identified the various active compounds present in the plant. The compound was later identified as a key chalcone derivative in licorice, contributing to its overall therapeutic properties. Its chemical structure and biological effects have been extensively studied in recent decades, making it a subject of interest in pharmacology and medicinal chemistry.

Isoliquiritigenin has been most studied for its potential anti-inflammatory and antioxidant properties. Research has shown that it can inhibit the activity of pro-inflammatory enzymes such as cyclooxygenase (COX) and lipoxygenase (LOX), which play a key role in the inflammatory response. This property suggests that isoliquiritigenin may be useful in managing chronic inflammatory diseases such as arthritis, inflammatory bowel disease (IBD), and even cardiovascular diseases. Furthermore, its antioxidant activity helps in neutralizing free radicals, reducing oxidative stress, and protecting cells from damage, which is beneficial in preventing age-related diseases and conditions like neurodegeneration and cancer.

In cancer research, isoliquiritigenin has shown promising anticancer effects. Studies have demonstrated that it can inhibit the proliferation of various cancer cell lines, including those of breast, liver, and lung cancer. The compound exerts its anticancer effects through several mechanisms, such as the induction of apoptosis (programmed cell death) in cancer cells, cell cycle arrest, and inhibition of metastasis. Additionally, isoliquiritigenin has been shown to suppress the expression of certain oncogenes and transcription factors involved in cancer cell survival and growth. These findings have made isoliquiritigenin a potential candidate for further research in the development of cancer therapies.

The compound also exhibits neuroprotective effects, which have been investigated in the context of neurodegenerative diseases like Alzheimer's and Parkinson's. In preclinical models, isoliquiritigenin has been shown to reduce the formation of amyloid plaques, a hallmark of Alzheimer's disease, and protect neuronal cells from oxidative damage. It is believed that its antioxidant and anti-inflammatory activities contribute to these neuroprotective effects, potentially offering a natural approach to the management of neurodegeneration.

In addition to its therapeutic potential, isoliquiritigenin has been explored for its use in the food and cosmetic industries. As an antioxidant, it helps in preserving the quality and shelf-life of food products, particularly those sensitive to oxidation. In cosmetics, it is used in skin care products for its skin-brightening, anti-aging, and anti-inflammatory properties. The compound is incorporated into topical formulations aimed at reducing skin pigmentation, promoting collagen production, and improving skin elasticity.

Despite the promising results from preclinical studies, further clinical trials are needed to fully establish the safety and efficacy of isoliquiritigenin in humans. However, its wide array of biological effects, coupled with its natural occurrence, makes it an appealing candidate for future therapeutic applications in medicine, nutrition, and cosmetics.

References

2010. Sensitivity and resistance towards isoliquiritigenin, doxorubicin and methotrexate in T cell acute lymphoblastic leukaemia cell lines by pharmacogenomics. Naunyn-Schmiedeberg's Archives of Pharmacology, 382(3).
DOI: 10.1007/s00210-010-0541-6

2009. Shallot and licorice constituent isoliquiritigenin arrests cell cycle progression and induces apoptosis through the induction of ATM/p53 and initiation of the mitochondrial system in human cervical carcinoma HeLa cells. Molecular Nutrition & Food Research, 53(7).
DOI: 10.1007/mnfr.200800288

2015. A protective mechanism of licorice (Glycyrrhiza uralensis): Isoliquiritigenin stimulates detoxification system via Nrf2 activation. Journal of Ethnopharmacology, 162.
DOI: 10.1016/j.jep.2014.12.043