Isoliquiritigenin (ISL) is a natural compound found in traditional herbal medicine. It belongs to the class of chalcones, which are precursors to the larger group of flavonoids commonly found in plants. Scientists are studying how this molecule interacts with human biological systems at a cellular level.
What Isoliquiritigenin Is and Where It Comes From
Isoliquiritigenin is a bioactive molecule naturally present in the roots of several species of Glycyrrhiza, most notably the licorice plant, Glycyrrhiza glabra. Chemically, it is classified as a chalcone, possessing a distinct open-chain structure that sets it apart from the closed-ring structure of typical flavonoids. This unique chemical arrangement, specifically identified as 2′,4,4′-Trihydroxychalcone, is responsible for its biological properties.
Licorice root has been a staple in traditional Chinese medicine for thousands of years. Through modern analytical techniques, Isoliquiritigenin has been singled out as a major active constituent and is now a focus of contemporary pharmacological research.
Cellular Mechanisms of Action
Isoliquiritigenin exerts its biological effects by modulating several interconnected signaling pathways within human cells, primarily revolving around the response to stress and inflammation. Its action as an antioxidant involves activating the Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. This pathway regulates the cellular defense system, prompting the cell to produce protective antioxidant enzymes like heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1).
ISL is also a strong modulator of inflammatory responses through its effect on the Nuclear Factor-kappa B (NF-κB) pathway. NF-κB is a protein complex that, when activated, triggers the production of pro-inflammatory molecules. Isoliquiritigenin suppresses this activation, dampening the inflammatory cascade.
ISL also interacts with the NOD-like receptor protein 3 (NLRP3) inflammasome, a multi-protein complex that initiates and regulates inflammatory responses. By inhibiting the NLRP3 inflammasome, ISL reduces the production of inflammatory signaling molecules like interleukin-1β (IL-1β).
Consumption and Supplementation Guidance
Isoliquiritigenin can be obtained through consuming whole licorice root or via isolated, standardized extracts. Consuming whole licorice introduces ISL along with hundreds of other compounds, including its precursor, isoliquiritin, which the gut microbiota converts into the active form. The amount of ISL absorbed can vary widely depending on the type of licorice, preparation method, and the individual’s gut bacteria.
When considering isolated ISL supplements, bioavailability is a major factor. Studies suggest that the oral bioavailability of ISL can be low, sometimes less than 12%, because it is rapidly metabolized in the liver and small intestine. The compound’s poor water solubility also limits its absorption, leading researchers to explore different delivery methods to enhance uptake.
The half-life of orally administered ISL is relatively short, often reported to be around 4 to 5 hours, meaning it is quickly metabolized and eliminated. Due to the lack of clinical trials establishing a standard human dose, there are no definitive consumption guidelines for ISL.
Safety Profile and Interactions
The safety profile of Isoliquiritigenin is often discussed in the context of its source, licorice root, which contains the triterpenoid saponin glycyrrhizin. High intake of glycyrrhizin is associated with pseudoaldosteronism, which can lead to adverse effects like high blood pressure, fluid retention, and low potassium levels. Consumers should look for supplements that specify they are “deglycyrrhizinated” if they are concerned about these side effects.
ISL itself is metabolized in the liver and small intestine, meaning it may potentially affect drug-metabolizing enzymes. Glycyrrhizin and its metabolite, glycyrrhetinic acid, are known to interact with various drug-metabolizing enzymes in the liver, such as certain Cytochrome P450 (CYP) enzymes, potentially altering the metabolism of concurrent medications. While ISL is a different molecule, any compound metabolized by the liver carries a theoretical potential for drug interactions, especially with medications that have a narrow therapeutic window. Consulting with a healthcare professional before combining ISL supplementation with prescription drugs is necessary to ensure safety and prevent unintended interactions.