Isoliquiritin

Isoliquiritin at a Glance

Isoliquiritin is a chalcone glucoside — the glucoside of the chalcone isoliquiritigenin — found in the roots of licorice (Glycyrrhiza species). It is a minor member of the yellow-pigmented flavonoid fraction that gives licorice root its colour, and it is almost always studied alongside its structural partner liquiritin, the flavanone glucoside to which it is chemically related.

Its most developed research story is antidepressant and neuroprotective: isolated isoliquiritin reduces immobility in mouse behavioural despair tests and protects nerve-like cells from stress-induced death, effects tied to raised brain monoamines and to suppression of inflammatory cell-death pathways ^{1,2,3Reference 1Li Y et al. · 2021Isoliquiritin ameliorates depression by suppressing NLRP3 inflammasome-mediated pyroptosis via miRNA-27a/SYK/NF-κB axisView study →Reference 2Wang W et al. · 2008AnimalAntidepressant-like effects of liquiritin and isoliquiritin from Glycyrrhiza uralensis in the forced swimming test and tail suspension test in miceView study →Reference 3Zhou YZ et al. · 2017Protective effect of isoliquiritin against corticosterone-induced neurotoxicity in PC12 cellsView study →}. Around that sit antioxidant, anti-inflammatory and some antitumour signals — but all of this is preclinical: isolated-molecule assays and rodent models, with no controlled human trials of isoliquiritin itself ^{6,7,8Reference 6Liu Y et al. · 2019Renoprotective effects of isoliquiritin against cationic bovine serum albumin-induced membranous glomerulonephritisView study →Reference 7Zhang XH et al. · 2021Isoliquiritin exert protective effect on telencephalon infarction injury by regulating multi-pathways in zebrafish model of ischemic strokeView study →Reference 8Wang J et al. · 2023Isoliquiritin modulates ferroptosis via NF-κB signaling inhibition and alleviates doxorubicin resistance in breast cancerView study →}.

As a minor flavonoid of a widely consumed food and medicinal plant, isoliquiritin carries a low toxicity flag. The prominent safety cautions attached to licorice — pseudoaldosteronism and raised blood pressure — belong to a different constituent, the saponin glycyrrhizin, not to this chalcone.

Isoliquiritin, Liquiritin & the Chalcone–Flavanone Pair

The single most useful thing to hold onto about this molecule is that it is one half of an isomeric pair. Licorice makes two closely related flavonoid glucosides:

• Isoliquiritin — an open-chain chalcone glucoside (aglycone: isoliquiritigenin), yellow-pigmented.
• Liquiritin — the cyclised flavanone glucoside (aglycone: liquiritigenin), colourless.

Chalcones and flavanones are constitutional isomers interconverted by opening or closing the flavonoid C-ring — in the plant this is catalysed by chalcone isomerase, and it can also happen chemically. So isoliquiritigenin (chalcone) and liquiritigenin (flavanone) are two forms of the same carbon skeleton, and their glucosides, isoliquiritin and liquiritin, mirror that relationship ^{10Reference 10Hasan MK et al. · 2021Phytochemistry, pharmacological activity, and potential health benefits of Glycyrrhiza glabraView study →}. This is why the two compounds co-occur, are hard to separate cleanly in extracts, and are so often co-studied — the foundational antidepressant paper tested both together ^{2Reference 2Wang W et al. · 2008AnimalAntidepressant-like effects of liquiritin and isoliquiritin from Glycyrrhiza uralensis in the forced swimming test and tail suspension test in miceView study →}.

Three distinctions are worth keeping straight, because the literature blurs them:

• Isoliquiritin (this one) = the chalcone glucoside.
• Isoliquiritigenin = its chalcone aglycone (no sugar) — more lipophilic, generally more potent in vitro, and the likely active form after gut hydrolysis.
• Isoliquiritin apioside = a related chalcone apioside (a different sugar) studied separately, e.g. in molecular-docking antiviral work — not the same molecule as isoliquiritin ^{9Reference 9Sinha SK et al. · 2021Potential leads from liquorice against SARS-CoV-2 main protease using molecular docking simulation studiesView study →}.

What It's Used For

Isoliquiritin’s evidence base is preclinical and mechanism-rich, and it splits by application. The load-bearing caveat is the compound-page discipline: this is the isolated molecule in vitro and in rodents, with no human trials — and it is chemically entangled with liquiritin in every whole-licorice study.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. There are no human data on the isolate, so all scores stay modest by design.

01Antidepressant / neuroprotectivePromising46%Mouse behavioural despair + monoamines ^{2Reference 2Wang W et al. · 2008AnimalAntidepressant-like effects of liquiritin and isoliquiritin from Glycyrrhiza uralensis in the forced swimming test and tail suspension test in miceView study →}; NLRP3/pyroptosis mechanism ^{1Reference 1Li Y et al. · 2021Isoliquiritin ameliorates depression by suppressing NLRP3 inflammasome-mediated pyroptosis via miRNA-27a/SYK/NF-κB axisView study →}; neuronal protection ^{3Reference 3Zhou YZ et al. · 2017Protective effect of isoliquiritin against corticosterone-induced neurotoxicity in PC12 cellsView study →}

02Anti-inflammatoryShaky40%Rodent colitis, atopic-dermatitis, membranous-nephritis isolate models via NF-κB/TLR4/JAK-STAT ^{4,5,6Reference 4Miao Z et al. · 2024AnimalIsoliquiritin ameliorates ulcerative colitis in rats through Caspase 3/HMGB1/TLR4 dependent signaling pathwayView study →Reference 5Wu Q et al. · 2022In vitroInhibitory effects of isoliquiritin on an atopic dermatitis model through the CD177/JAK2/STAT pathway in vitro and in vivoView study →Reference 6Liu Y et al. · 2019Renoprotective effects of isoliquiritin against cationic bovine serum albumin-induced membranous glomerulonephritisView study →}

03Antioxidant / cytoprotectiveShaky36%In-vitro + zebrafish/rodent: Nrf2, ↑SOD/GSH-Px, ↓MDA/ROS ^{3,6,7Reference 3Zhou YZ et al. · 2017Protective effect of isoliquiritin against corticosterone-induced neurotoxicity in PC12 cellsView study →Reference 6Liu Y et al. · 2019Renoprotective effects of isoliquiritin against cationic bovine serum albumin-induced membranous glomerulonephritisView study →Reference 7Zhang XH et al. · 2021Isoliquiritin exert protective effect on telencephalon infarction injury by regulating multi-pathways in zebrafish model of ischemic strokeView study →}

04AntitumourShaky28%Breast-cancer cells + nude mice: pro-ferroptosis, doxorubicin re-sensitisation ^{8Reference 8Wang J et al. · 2023Isoliquiritin modulates ferroptosis via NF-κB signaling inhibition and alleviates doxorubicin resistance in breast cancerView study →}

05Antiviral (in-silico)Shaky14%Molecular-docking against SARS-CoV-2 Mpro (apioside form), no wet-lab confirmation ^{9Reference 9Sinha SK et al. · 2021Potential leads from liquorice against SARS-CoV-2 main protease using molecular docking simulation studiesView study →}

Mechanisms

The recurring pair — Nrf2 up, NF-κB down — is the throughline that ties the antidepressant, anti-inflammatory, antioxidant and even the pro-ferroptotic anticancer findings together; the monoamine effect is the one mechanism specific to the mood story.

Pharmacokinetics

Isoliquiritin is a flavonoid glucoside, and that governs its pharmacokinetics. Like most polar glucosides it is poorly absorbed intact: LC-MS/MS and HPLC-MS/MS studies detect it in rat plasma only at low ng/mL concentrations after oral dosing of licorice-containing formulas ^{11,12Reference 11Li L et al. · 2007AnimalSimultaneous quantification of multiple licorice flavonoids in rat plasmaView study →Reference 12Wang T et al. · 2016AnimalSimultaneous quantification of catechin, epicatechin, liquiritin, isoliquiritin, and related compounds in rat plasma by HPLC-MS/MSView study →}. The pharmacologically relevant species is therefore likely the aglycone, isoliquiritigenin, liberated by gut-microbial β-glucosidases and better able to cross membranes — the same deglycosylation-then-absorption pattern seen for liquiritin and other flavonoid glucosides. Robust isolate ADME — oral bioavailability, Cmax, half-life, tissue distribution, and the quantitative isoliquiritin→isoliquiritigenin conversion — has not been characterised, which is a real limit on interpreting the in-vitro potencies above ^{11,12Reference 11Li L et al. · 2007AnimalSimultaneous quantification of multiple licorice flavonoids in rat plasmaView study →Reference 12Wang T et al. · 2016AnimalSimultaneous quantification of catechin, epicatechin, liquiritin, isoliquiritin, and related compounds in rat plasma by HPLC-MS/MSView study →}.

Clinical Trials

There are no controlled human trials of isolated isoliquiritin. The human evidence that exists is for whole licorice or licorice-flavonoid extracts, within which isoliquiritin is one minor, co-eluting flavonoid — not an isolate result.

Last checked: July 2026.

Isolate vs. Plant Studies

Isoliquiritin sits at an unusually clean isolate end for its mechanistic work and an unusually murky one for anything human. The antidepressant, anti-inflammatory, antioxidant and antitumour studies almost all test the purified molecule in cells or rodents ^{1,2,4,5,6,7,8Reference 1Li Y et al. · 2021Isoliquiritin ameliorates depression by suppressing NLRP3 inflammasome-mediated pyroptosis via miRNA-27a/SYK/NF-κB axisView study →Reference 2Wang W et al. · 2008AnimalAntidepressant-like effects of liquiritin and isoliquiritin from Glycyrrhiza uralensis in the forced swimming test and tail suspension test in miceView study →Reference 4Miao Z et al. · 2024AnimalIsoliquiritin ameliorates ulcerative colitis in rats through Caspase 3/HMGB1/TLR4 dependent signaling pathwayView study →Reference 5Wu Q et al. · 2022In vitroInhibitory effects of isoliquiritin on an atopic dermatitis model through the CD177/JAK2/STAT pathway in vitro and in vivoView study →Reference 6Liu Y et al. · 2019Renoprotective effects of isoliquiritin against cationic bovine serum albumin-induced membranous glomerulonephritisView study →Reference 7Zhang XH et al. · 2021Isoliquiritin exert protective effect on telencephalon infarction injury by regulating multi-pathways in zebrafish model of ischemic strokeView study →Reference 8Wang J et al. · 2023Isoliquiritin modulates ferroptosis via NF-κB signaling inhibition and alleviates doxorubicin resistance in breast cancerView study →} — a genuine strength for attributing an effect to this compound. But there is no human trial of the isolate at all, so the only human-scale evidence is whole licorice, where isoliquiritin is a minor flavonoid among glycyrrhizin, liquiritin, glabridin, the licochalcones and dozens of others, and where it cannot be cleanly separated from its isomer liquiritin. Two practical consequences: the mouse antidepressant work dosed both glucosides together ^{2Reference 2Wang W et al. · 2008AnimalAntidepressant-like effects of liquiritin and isoliquiritin from Glycyrrhiza uralensis in the forced swimming test and tail suspension test in miceView study →}, and any whole-licorice benefit cannot be assigned to isoliquiritin specifically.

Prevalence in Nature

Isoliquiritin is a characteristic chalcone glucoside of the genus Glycyrrhiza, reported from G. glabra, G. uralensis (Chinese licorice) and G. inflata ^{10Reference 10Hasan MK et al. · 2021Phytochemistry, pharmacological activity, and potential health benefits of Glycyrrhiza glabraView study →}. It belongs to the root’s total-flavonoid fraction, roughly 1–1.5% of the dried root, and as a yellow chalcone it contributes to the pigment of licorice root; individual flavonoid levels vary with species and chemotype, provenance and extraction, the same variables that drive the rest of licorice’s chemistry. A reliable isolate-specific dry-weight figure for isoliquiritin is not well quantified in the accessible literature — it is consistently described as a minor constituent rather than a dominant one, and it is not established as occurring outside Glycyrrhiza ^{10Reference 10Hasan MK et al. · 2021Phytochemistry, pharmacological activity, and potential health benefits of Glycyrrhiza glabraView study →}.

Discovery & Synthesis

Isoliquiritin was characterised as the chalcone-glucoside counterpart of liquiritin among the principal flavonoids of licorice, the pair having been studied since the mid-twentieth century as the yellow (chalcone) and colourless (flavanone) forms of the same skeleton ^{10Reference 10Hasan MK et al. · 2021Phytochemistry, pharmacological activity, and potential health benefits of Glycyrrhiza glabraView study →}. It is obtained today chiefly by extraction and chromatographic isolation from licorice root for research use; a dedicated first total synthesis is not well documented, and the compound is not manufactured at scale — where a defined chalcone is wanted, the aglycone isoliquiritigenin is the more common synthetic target. Biosynthetically it arises on the flavonoid pathway, with chalcone isomerase governing the chalcone↔flavanone equilibrium that links it to liquiritin.

Patents: not yet researched.

Toxicity & Safety

Isoliquiritin carries a low toxicity flag: it is a minor flavonoid of licorice, a plant eaten and used medicinally for millennia, and the isolate has shown a cytoprotective rather than cytotoxic profile in normal cells across the studies above ^{3,6,7Reference 3Zhou YZ et al. · 2017Protective effect of isoliquiritin against corticosterone-induced neurotoxicity in PC12 cellsView study →Reference 6Liu Y et al. · 2019Renoprotective effects of isoliquiritin against cationic bovine serum albumin-induced membranous glomerulonephritisView study →Reference 7Zhang XH et al. · 2021Isoliquiritin exert protective effect on telencephalon infarction injury by regulating multi-pathways in zebrafish model of ischemic strokeView study →}. The notable safety caveat is one of attribution, not of the molecule itself.

Safety at a Glance

✅ Low / no toxicity

• A low-toxicity food-plant flavonoid. A minor constituent of licorice with a cytoprotective, antioxidant profile in normal cells; no isolate toxicity signal in the reviewed models ^{3,6,7Reference 3Zhou YZ et al. · 2017Protective effect of isoliquiritin against corticosterone-induced neurotoxicity in PC12 cellsView study →Reference 6Liu Y et al. · 2019Renoprotective effects of isoliquiritin against cationic bovine serum albumin-induced membranous glomerulonephritisView study →Reference 7Zhang XH et al. · 2021Isoliquiritin exert protective effect on telencephalon infarction injury by regulating multi-pathways in zebrafish model of ischemic strokeView study →}.
• Human data are absent. Every finding is in-vitro or rodent isolate work (or whole extract); there are no human trials of isoliquiritin, and its oral bioavailability as a glucoside is likely low ^{11,12Reference 11Li L et al. · 2007AnimalSimultaneous quantification of multiple licorice flavonoids in rat plasmaView study →Reference 12Wang T et al. · 2016AnimalSimultaneous quantification of catechin, epicatechin, liquiritin, isoliquiritin, and related compounds in rat plasma by HPLC-MS/MSView study →}.
• Do not inherit licorice’s marquee risk. Pseudoaldosteronism, potassium loss and raised blood pressure from heavy licorice use are caused by the saponin glycyrrhizin, not by this chalcone — but they still apply to whole-licorice intake.
• Interactions not characterised for the isolate. No CYP/transporter or drug-interaction dataset exists specifically for isoliquiritin; whole-licorice interaction cautions should be read at the herb level.

Reproductive and developmental data for the isolated molecule are not established; as a plant-constituent phytochemistry page this does not issue a pregnancy or lactation verdict — that decision belongs to the licorice herb page and any product page, where intake is actually decided.

Dosage

There is no established or recommended human dose for isolated isoliquiritin. The only quantified figures are preclinical: the mouse antidepressant work used oral isoliquiritin at 10, 20 and 40 mg/kg ^{2Reference 2Wang W et al. · 2008AnimalAntidepressant-like effects of liquiritin and isoliquiritin from Glycyrrhiza uralensis in the forced swimming test and tail suspension test in miceView study →}, and the other activities come from in-vitro concentrations and rodent/zebrafish doses that do not convert to human self-dosing.

Human exposure to isoliquiritin is indirect — through eating licorice or taking licorice/flavonoid extracts, where it is one minor flavonoid among many. These are doses studied in research and are not a personal recommendation.

References

1. Li Y, et al. (2021). Isoliquiritin ameliorates depression by suppressing NLRP3 inflammasome-mediated pyroptosis via miRNA-27a/SYK/NF-κB axis. Journal of Neuroinflammation. https://pubmed.ncbi.nlm.nih.gov/33402173/
2. Wang W, et al. (2008). Antidepressant-like effects of liquiritin and isoliquiritin from Glycyrrhiza uralensis in the forced swimming test and tail suspension test in mice. Progress in Neuro-Psychopharmacology & Biological Psychiatry. https://pubmed.ncbi.nlm.nih.gov/18289754/
3. Zhou YZ, et al. (2017). Protective effect of isoliquiritin against corticosterone-induced neurotoxicity in PC12 cells. Food & Function. https://pubmed.ncbi.nlm.nih.gov/28229156/
4. Miao Z, et al. (2024). Isoliquiritin ameliorates ulcerative colitis in rats through Caspase 3/HMGB1/TLR4 dependent signaling pathway. Current Gene Therapy. https://pubmed.ncbi.nlm.nih.gov/37526181/
5. Wu Q, et al. (2022). Inhibitory effects of isoliquiritin on an atopic dermatitis model through the CD177/JAK2/STAT pathway in vitro and in vivo. Annals of Translational Medicine. https://pubmed.ncbi.nlm.nih.gov/36267759/
6. Liu Y, et al. (2019). Renoprotective effects of isoliquiritin against cationic bovine serum albumin-induced membranous glomerulonephritis. Drug Design, Development and Therapy. https://pubmed.ncbi.nlm.nih.gov/31802848/
7. Zhang XH, et al. (2021). Isoliquiritin exert protective effect on telencephalon infarction injury by regulating multi-pathways in zebrafish model of ischemic stroke. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/33535128/
8. Wang J, et al. (2023). Isoliquiritin modulates ferroptosis via NF-κB signaling inhibition and alleviates doxorubicin resistance in breast cancer. Immunopharmacology and Immunotoxicology. https://pubmed.ncbi.nlm.nih.gov/36605015/
9. Sinha SK, et al. (2021). Potential leads from liquorice against SARS-CoV-2 main protease using molecular docking simulation studies. Combinatorial Chemistry & High Throughput Screening. https://pubmed.ncbi.nlm.nih.gov/32807047/
10. Hasan MK, et al. (2021). Phytochemistry, pharmacological activity, and potential health benefits of Glycyrrhiza glabra. Heliyon. https://pubmed.ncbi.nlm.nih.gov/34189299/
11. Li L, et al. (2007). Simultaneous quantification of multiple licorice flavonoids in rat plasma. Journal of the American Society for Mass Spectrometry. https://pubmed.ncbi.nlm.nih.gov/17291779/
12. Wang T, et al. (2016). Simultaneous quantification of catechin, epicatechin, liquiritin, isoliquiritin, and related compounds in rat plasma by HPLC-MS/MS. Biomedical Chromatography. https://pubmed.ncbi.nlm.nih.gov/26613237/

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