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Isoliquiritigenin – Effects, Sources & Research

Isoliquiritigenin is a natural plant compound from licorice root with antioxidant, anti-inflammatory, and cancer-preventive properties.

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Things worth knowing about "Isoliquiritigenin"

Isoliquiritigenin is a natural plant compound from licorice root with antioxidant, anti-inflammatory, and cancer-preventive properties.

What is Isoliquiritigenin?

Isoliquiritigenin is a chalcone – a subclass of flavonoids – found naturally in the root of the licorice plant (Glycyrrhiza glabra, Glycyrrhiza uralensis). It is a yellow-colored, polyphenolic secondary plant metabolite with a long history of use in traditional Chinese and Ayurvedic medicine. Chemically, isoliquiritigenin is an α,β-unsaturated ketone with a characteristic open-chain chalcone structure, which distinguishes it from ring-closed flavonoids such as flavanones.

Sources and Occurrence

The compound is primarily obtained from the following plants:

Licorice root (Glycyrrhiza glabra and Glycyrrhiza uralensis) – primary source
Licorice fruits and extracts
Certain legumes such as soybeans and chickpeas (in small amounts)
Sorghum (Sorghum bicolor)

In food and dietary supplements, isoliquiritigenin most commonly occurs as a component of licorice extracts.

Mechanisms of Action

Antioxidant Activity

Isoliquiritigenin scavenges free radicals via its phenolic hydroxyl group and activates the Nrf2 signaling pathway (Nuclear factor erythroid 2-related factor 2), which upregulates the production of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase. This protects cells from oxidative stress and damage.

Anti-inflammatory Activity

The compound inhibits the NF-κB signaling pathway (Nuclear Factor kappa-light-chain-enhancer of activated B cells), a central regulator of inflammatory responses. This reduces the release of pro-inflammatory mediators such as TNF-α, IL-1β, and IL-6. In addition, isoliquiritigenin suppresses cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS).

Antitumor Properties

Numerous laboratory studies have shown that isoliquiritigenin can induce apoptosis (programmed cell death) and inhibit the proliferation of cancer cells. This effect has been described in various cancer cell lines, including breast, colorectal, hepatic, and lung cancer cells. The underlying mechanisms involve caspase activation, regulation of the Bcl-2 protein family, and inhibition of cell cycle-regulating proteins.

Additional Mechanisms

Phytoestrogenic activity: Isoliquiritigenin binds weakly to estrogen receptors, producing hormone-like effects.
Neuroprotective effects: Animal studies have reported protective effects on nerve cells, partly through inhibition of neuroinflammation.
Antidiabetic effects: Early studies suggest improvements in insulin sensitivity and inhibition of α-glucosidase.
Antimicrobial activity: Laboratory experiments have demonstrated activity against certain bacteria and fungi.

Medical Applications and Current Research

Isoliquiritigenin is currently in a predominantly preclinical research stage. Most studies have been conducted in cell cultures or animal models. Clinical trials in humans are still limited, so definitive therapeutic recommendations for human use have not yet been established. Nevertheless, scientific interest in this compound remains high due to its promising potential in cancer prevention, anti-inflammatory therapy, and metabolic regulation.

Dosage and Administration

There are currently no officially established dosage recommendations for isolated isoliquiritigenin in humans. Dosage guidance for licorice products is, however, available in the context of licorice root extracts as a whole. The European Food Safety Authority (EFSA) recommends avoiding a daily intake of more than 100 mg glycyrrhizin (the main active compound in licorice root), as higher amounts may cause adverse effects. Isoliquiritigenin itself is typically present in much smaller quantities than glycyrrhizin in most licorice extracts.

Safety and Side Effects

At the doses tested in preclinical studies, isoliquiritigenin appears to be relatively well tolerated. However, the following points should be considered:

When consumed as part of licorice extracts at high doses, hypokalemia (low blood potassium), elevated blood pressure, and edema may occur (primarily attributed to glycyrrhizin, not isoliquiritigenin itself).
Due to its mild phytoestrogenic properties, individuals with hormone-sensitive conditions (e.g., certain forms of breast cancer) should consult a healthcare professional before use.
There are no reliable safety data for high-dose isoliquiritigenin preparations in pregnant or breastfeeding women.
Interactions with certain medications (particularly antihypertensives and cardiac drugs) are possible.

References

Zhu S. et al. (2021): Isoliquiritigenin: A mechanistic review of its pharmacological activity. Biomedicine & Pharmacotherapy, 143, 112090. DOI: 10.1016/j.biopha.2021.112090
European Food Safety Authority (EFSA) (2008): Scientific Opinion on the safety in use of liquorice root extract as a food ingredient. EFSA Journal, 6(12), 884.
Wang C. et al. (2018): Biological activities of isoliquiritigenin: an updated review. Journal of Pharmacy and Pharmacology, 70(10), 1258-1273. DOI: 10.1111/jphp.12983

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