# Licochalcone (Glycyrrhiza spp.)

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/licochalcone-glycyrrhiza-spp
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-04-02
**Evidence Score:** 1 / 10
**Category:** Compound
**Also Known As:** Licochalcone (Glycyrrhiza uralensis / Glycyrrhiza glabra), Licochalcone A, Licochalcone B, 4-methoxy-2′,4′-dihydroxychalcone, Lico A, LicB, oxygenated chalcone, Glycyrrhiza chalcone

## Overview

Licochalcones A through G are α,β-unsaturated ketone chalcone compounds derived from Glycyrrhiza licorice roots that exert [anti-inflammatory](/ingredients/condition/inflammation), anticancer, [antimicrobial](/ingredients/condition/immune-support), and antimalarial effects by suppressing NF-κB, modulating PI3K/Akt/mTOR, and activating Nrf2/HO-1 signaling cascades. Licochalcone A demonstrated in vivo antimalarial activity sufficient to eradicate Plasmodium yoelii infection in murine models, while Licochalcone B achieved IC50 values as low as 8.78 μM for nitric oxide inhibition and 9.67 μM against certain cancer cell lines in preclinical studies.

## Health Benefits

- **Anti-Inflammatory Activity**: Licochalcone A suppresses NF-κB nuclear translocation and inhibits production of [pro-inflammatory cytokine](/ingredients/condition/inflammation)s, TNF-α, IL-6, and nitric oxide in macrophage models such as RAW264.7 cells, reducing inflammatory signaling at concentrations of 5–80 μM.
- **Anticancer Potential**: Licochalcone B inhibits cancer cell proliferation with IC50 values ranging from 9.67 to 110.15 μM across multiple cell lines by inducing caspase-3/9 activation, Bax upregulation, cytochrome C release, p53 stabilization, and G2/M cell cycle arrest.
- **Antimalarial Action**: Licochalcone A displays antiprotozoal activity against Plasmodium species, with in vivo studies demonstrating complete eradication of P. yoelii infection in mice, making it one of the few plant-derived chalcones with documented in vivo antimalarial efficacy.
- **Antioxidant Defense**: Licochalcone B potently activates the Nrf2/HO-1/NQO1 antioxidant response pathway while downregulating Keap1 expression, and demonstrates direct ROS scavenging with low cytotoxicity at studied concentrations, supporting cytoprotective effects in [oxidative stress](/ingredients/condition/antioxidant) models.
- **[Hepatoprotective](/ingredients/condition/detox) Effects**: Extracts standardized for licochalcone content from Glycyrrhiza spp. are associated with hepatoprotective bioactivity in preclinical models, attributed in part to NF-κB suppression, antioxidant pathway activation, and attenuation of hepatic inflammatory cytokine cascades.
- **[Antimicrobial](/ingredients/condition/immune-support) and Antiviral Properties**: Licochalcones exhibit broad-spectrum antimicrobial activity against bacterial and fungal pathogens and demonstrate antiviral effects in cell-based assays, mechanisms proposed to involve membrane disruption and inhibition of viral replication enzymes.
- **[Neuroprotective](/ingredients/condition/cognitive) Activity**: Licochalcone A modulates the Nrf2/MAPK axis via non-coding RNA regulation including miR-144, and inhibits JNK/p38 MAPK pathways, suggesting potential in attenuating neuroinflammation and oxidative neuronal damage in preclinical models.

## Mechanism of Action

Licochalcone A inhibits NF-κB activation by blocking IκB phosphorylation and nuclear translocation of the p65 subunit, simultaneously targeting JNK, p38 MAPK, and PI3K/Akt/mTOR pathways to suppress [cytokine](/ingredients/condition/inflammation) gene expression and induce mitochondria-dependent apoptosis through ROS accumulation, LC3-II [autophagy](/ingredients/condition/longevity) activation, and G0/G1 or G2/M cell cycle arrest; it also upregulates ADAM9 expression via MEK-ERK signaling and suppresses Sp1 transcription factor activity in cancer cells. Licochalcone B distinctly inhibits NF-κB by targeting protein kinase A-mediated phosphorylation of p65 at Ser276, and inhibits 15-lipoxygenase by engaging active-site residues including Thr412 and Arg415, thereby reducing PGE2, leukotriene, and NO biosynthesis. Both compounds share structural activation of the Keap1/Nrf2/HO-1/NQO1 cytoprotective axis, downregulating Keap1 to permit Nrf2 nuclear entry and transcription of [antioxidant](/ingredients/condition/antioxidant) response element genes. The α,β-unsaturated ketone Michael acceptor pharmacophore shared across all licochalcone congeners is considered central to their covalent interaction with cysteine residues on target proteins including Keap1, contributing to both therapeutic bioactivity and the need for careful evaluation of off-target reactivity.

## Clinical Summary

No human clinical trials investigating licochalcone isolates as primary interventions have been reported in the indexed scientific literature; all documented efficacy data originates from in vitro and murine in vivo experimental models. Key outcomes studied preclinically include tumor cell viability (IC50 values of 8.78–110.15 μM for Licochalcone B), nitric oxide and [cytokine](/ingredients/condition/inflammation) suppression in macrophage assays, and complete P. yoelii eradication in mice for Licochalcone A. While these findings are scientifically promising, the absence of human pharmacokinetic data, bioavailability assessments, and clinical endpoints means confidence in translatable human efficacy remains very low. Regulatory and scientific bodies have not established any clinical dosing recommendations, and the compound should currently be considered investigational.

## Nutritional Profile

Licochalcones are secondary metabolites present in trace quantities within Glycyrrhiza root matrix, which itself contains glycyrrhizin (2–9% dry weight), flavonoids including liquiritin and isoliquiritin, polysaccharides, amino acids, and minerals. Licochalcone A and related congeners constitute a small fraction of the total chalcone content, typically below 1% of dry root weight, with exact concentrations varying by species, geographic origin, harvest age, and extraction method. As isolated compounds, licochalcones have no macronutrient or micronutrient significance; their biological relevance is entirely as bioactive phytochemicals. Oral bioavailability of licochalcone A has not been rigorously characterized in humans, though the α,β-unsaturated ketone motif raises considerations about first-pass [metabolism](/ingredients/condition/weight-management) and potential reactivity with [glutathione](/ingredients/condition/detox).

## Dosage & Preparation

- **Root Extract Powder**: Licochalcones are present in Glycyrrhiza root extracts; standardized extracts specifying licochalcone A or B percentage content are available for research but no human supplemental dose has been established.
- **Research Concentrations (In Vitro)**: Licochalcone A has been studied at 5–125 μM in cell models; Licochalcone B at concentrations achieving IC50 of 8.78 μM (NO inhibition) to 110.15 μM (cancer cell lines) — these are not equivalent to oral human doses.
- **Traditional Root Preparation**: Glycyrrhiza roots are traditionally decocted (boiled in water for 20–30 minutes) or tinctured in ethanol; licochalcone content in such preparations has not been standardized for human therapeutic use.
- **No Established Human Dose**: No regulatory authority or clinical guideline has defined a safe and effective supplemental dose for isolated licochalcone compounds; use outside of research settings lacks evidence-based dosing guidance.
- **Standardization Note**: Commercial licorice extracts are more commonly standardized for glycyrrhizin content (typically 18–22%), not licochalcone concentration, making chalcone-specific dosing from conventional products unreliable.

## Safety & Drug Interactions

Hepatotoxic effects have been noted among the biological activities attributed to licochalcone-containing preparations, though dose-response relationships and specific mechanisms responsible for hepatotoxicity in humans have not been characterized; the α,β-unsaturated ketone Michael acceptor structure common to all licochalcones raises theoretical concerns about covalent protein adduct formation and idiosyncratic toxicity. Licochalcone B demonstrated relatively low cytotoxicity in vitro at active concentrations (IC50 ~110.15 μM in some cell models), but in vitro cytotoxicity profiles do not reliably predict human safety outcomes. No formal drug interaction studies exist for isolated licochalcones; however, given their modulation of CYP enzyme-relevant pathways (PI3K/Akt, [NF-κB](/ingredients/condition/inflammation)), caution is warranted in individuals taking anticoagulants, immunosuppressants, or chemotherapeutic agents. Pregnancy and lactation safety data are entirely absent, and use during pregnancy should be avoided given the lack of any human safety evidence; individuals with liver disease should exercise particular caution.

## Scientific Research

The evidence base for licochalcones consists almost entirely of in vitro cell culture studies and in vivo rodent experiments, with no published randomized controlled clinical trials reporting human pharmacokinetic, efficacy, or safety data as of available literature. In vitro studies have employed cancer cell lines, RAW264.7 macrophages, and hepatocyte models, establishing IC50 values and pathway mechanistic data for Licochalcone A and B, while the antimalarial activity of Licochalcone A has been confirmed in P. yoelii-infected mouse models representing a meaningful step toward in vivo validation. Systematic reviews and narrative reviews of the licochalcone class acknowledge the breadth of bioactivities documented across multiple in vitro systems but explicitly call for pharmacokinetic studies, toxicity profiling, and ultimately human clinical trials before therapeutic claims can be substantiated. The overall evidence quality is preclinical, and effect sizes observed in cell-based assays at micromolar concentrations cannot be directly extrapolated to human therapeutic doses without absorption, distribution, [metabolism](/ingredients/condition/weight-management), and excretion data.

## Historical & Cultural Context

Glycyrrhiza root — the botanical source of licochalcones — carries one of the longest documented histories of medicinal use in the world, appearing in ancient Egyptian, Assyrian, and Chinese pharmacopoeias dating back over 3,000 years. In Traditional Chinese Medicine, Gan Cao (G. uralensis) is among the most frequently prescribed herbs, used to harmonize formulas, soothe [inflammatory](/ingredients/condition/inflammation) conditions of the respiratory and gastrointestinal tract, and tonify qi, though this historical use applied to the whole root and its glycyrrhizin and flavonoid complex rather than isolated chalcones. Ayurvedic medicine employed yashtimadhu (G. glabra) for respiratory ailments, peptic ulcers, and as a rasayana [adaptogen](/ingredients/condition/stress). The isolation and characterization of licochalcone A as a distinct bioactive compound did not occur until modern phytochemical research in the late twentieth century, meaning its specific pharmacological properties were not distinguished from the broader root profile in historical practice.

## Synergistic Combinations

Licochalcone A has been investigated alongside other Glycyrrhiza-derived constituents including glycyrrhizin and liquiritigenin, where combinatorial [anti-inflammatory](/ingredients/condition/inflammation) effects suggest additive to synergistic NF-κB suppression, though formal combination pharmacology data in humans is lacking. The Nrf2 pathway activation shared by Licochalcone B and other polyphenolic compounds such as sulforaphane or quercetin suggests potential mechanistic synergy when combined with other Nrf2 activators, potentially allowing lower individual doses for [antioxidant](/ingredients/condition/antioxidant) cellular protection. In antimalarial research contexts, chalcone scaffolds including licochalcone A have been explored in combination with conventional antimalarials to address drug-resistant Plasmodium strains, though no clinical combination protocols have been established.

## Frequently Asked Questions

### What is licochalcone and where does it come from?

Licochalcones (A through G) are oxygenated chalcone polyphenolic compounds isolated from the roots of Glycyrrhiza licorice species, particularly G. inflata, G. glabra, and G. uralensis. They are structurally defined by two aromatic rings connected by an α,β-unsaturated ketone bridge and are classified as flavonoid precursors. Their concentration in licorice root is low and varies by species, growing region, and extraction method.

### What does licochalcone A do in the body?

Licochalcone A suppresses the NF-κB inflammatory signaling pathway by blocking IκB phosphorylation, and modulates JNK, p38 MAPK, and PI3K/Akt/mTOR cascades to reduce cytokine production, induce cancer cell apoptosis, and activate antioxidant responses via Nrf2. It has also demonstrated antimalarial activity in mouse models by eradicating Plasmodium yoelii infection. All established actions are from preclinical (in vitro and animal) research; no human clinical data currently exists.

### Is licochalcone safe to take as a supplement?

There is insufficient human safety data to confirm licochalcone is safe as a standalone supplement; hepatotoxic effects have been noted in biological activity reviews, and the compound's α,β-unsaturated ketone structure raises theoretical concerns about reactive protein adduct formation. No regulatory agency has established a safe human dose for isolated licochalcones. Individuals with liver disease, those who are pregnant or breastfeeding, or those taking medications including anticoagulants or chemotherapy should avoid use until human safety studies are available.

### What is the difference between licochalcone A and licochalcone B?

Licochalcone A and B are structurally related but pharmacologically distinct congeners from Glycyrrhiza roots. Licochalcone A is most noted for its antimalarial activity in animal models and NF-κB/MAPK-mediated anti-inflammatory and anticancer effects, while Licochalcone B is distinguished by its inhibition of 15-lipoxygenase (targeting Thr412 and Arg415 residues), PKA-mediated NF-κB suppression at Ser276, and potent nitric oxide inhibition with an IC50 of approximately 8.78 μM. Both activate the Nrf2/HO-1/NQO1 antioxidant pathway, but their specific molecular targets and potency profiles differ across biological assays.

### Has licochalcone been tested in human clinical trials?

As of currently available published literature, no human clinical trials have been conducted with isolated licochalcone compounds as the primary intervention, and no sample sizes, effect sizes, or human pharmacokinetic data have been reported. All efficacy evidence derives from in vitro cell culture experiments and in vivo rodent studies. Scientific reviewers in the field have explicitly identified the lack of human clinical validation as a critical gap, and licochalcones should currently be considered investigational compounds rather than clinically established therapeutics.

### What food sources contain licochalcone naturally?

Licochalcone is primarily found in licorice root (Glycyrrhiza species), particularly in dried licorice extracts and licorice preparations used in traditional medicine. While licorice is used as a flavoring agent in candies, beverages, and herbal teas, the licochalcone content in these consumer products is typically much lower than in concentrated licorice root extracts. Consuming licorice-flavored foods alone may not provide sufficient licochalcone to achieve the anti-inflammatory or bioactive effects observed in clinical studies.

### How does licochalcone absorption work, and what affects how much your body can use?

Licochalcone bioavailability is influenced by its lipophilic (fat-soluble) nature, meaning absorption may be enhanced when taken with dietary fat or in formulations designed to improve solubility. The gut microbiota and individual metabolic differences can also affect how efficiently licochalcone is absorbed and utilized by the body. Licorice extracts standardized for licochalcone content typically show better bioavailability compared to whole licorice root due to higher concentration of the active compound.

### Who should avoid licochalcone supplementation, and are there specific populations at higher risk?

Individuals with hypertension, heart disease, or kidney conditions should consult a healthcare provider before using licochalcone supplements, as licorice root—the source of licochalcone—can affect electrolyte balance and blood pressure in sensitive populations. Pregnant and breastfeeding women should avoid licochalcone supplementation due to limited safety data and potential effects on hormone metabolism. Those taking medications for blood pressure, corticosteroids, or hormone-sensitive conditions should seek medical guidance before supplementing, as licorice compounds can potentiate or interfere with these treatments.

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