Isoliquiritigenin: A Comprehensive Reference
1. Identity and Chemical Characterization
1.1 Nomenclature and Chemical Structure
Isoliquiritigenin (2′,4′,4-trihydroxychalcone, ISL) is extracted from licorice root and has a chalcone structure. Chemically, isoliquiritigenin is a chalcone, specifically 4,2′,4′-trihydroxychalcone. Chalcones are an open-chain subclass of flavonoids, differing from the more common closed-ring flavonoid structures. Its molecular formula is C₁₅H₁₂O₄, and it is registered in PubChem under Compound ID 638278. It is also referred to by the abbreviations ISL and ILG in the scientific literature. Among the many bioactive constituents of Glycyrrhiza root — including chalcones (isoliquiritin, isoliquiritin apioside, licuraside, and licochalcone A), isoflavonoids (licoricidin and glabridin), flavanones (liquiritin, liquiritin apioside, and liquiritigenin), the triterpene glycyrrhetinic acid, and the saponin glycyrrhizin — isoliquiritigenin (ILG) represents one of the most pharmacologically important components of the Glycyrrhiza root.
1.2 Botanical Sources
Isoliquiritigenin (ISL) is one of the bioactive ingredients isolated from the roots of plants belonging to licorice, including Glycyrrhiza uralensis, Mongolian glycyrrhiza, Glycyrrhiza glabra, and so forth. Licorice is an ancient medicinal herb constituting three main species: Glycyrrhiza glabra L., Glycyrrhiza uralensis Fish. ex DC., and Glycyrrhiza inflata Batalin. Isoliquiritigenin also exists in vegetables including shallots and bean sprouts. The yellow coloration of Dahlia variabilis flowers is mainly due to the presence of 4′-malonylglucosides of the 6′-deoxychalcones isoliquiritigenin and butein.
1.3 Common Forms and Preparations
Isoliquiritigenin is present in various commercial products, often as a component of licorice root extracts. These extracts are commonly found in skincare formulations, where their skin-lightening and soothing properties are utilized. It is also included in some dietary supplements, typically as part of a multi-ingredient botanical blend. Licorice is used as a flavoring agent in candy, gum, tobacco, toothpaste, cough mixtures, herbal teas, and other beverages. In research contexts, ISL is used as a purified isolate. Several approaches, including self-nanoemulsifying drug delivery systems (SNEDDS) and nanoparticles, are being explored to address the challenge of limited oral absorption and bioavailability associated with ISL. The U.S. Food and Drug Administration (FDA) classifies licorice and licorice extracts/derivatives as generally recognized as safe (GRAS) for use in foods (21 CFR 184.1408) and animal feeds (21 CFR 582.10; 582.20). They are also FDA-approved for use in certain over-the-counter drugs (21 CFR 310.528; 310.544; 310.545).
2. Traditional and Historical Use
2.1 Traditional Chinese Medicine
Licorice, the roots and rhizomes of Glycyrrhiza uralensis, Glycyrrhiza radix, and Glycyrrhiza glabra, is one of the most studied Chinese herbs due to its extensive pharmacological activities. This herb has been used in traditional Chinese medicine clinical practice for more than two thousand years. Since 25 A.D., licorice has been extensively used by the Chinese to tonify qi (life energy) of the heart and spleen. Derived from the dried root and rhizome of Glycyrrhiza glabra L., Glycyrrhiza uralensis Fisch., or Glycyrrhiza inflata Bat., the use of licorice is deeply ingrained in TCM theory, with the belief that "nine out of ten formulas contain licorice." The genus Glycyrrhiza is a small perennial herb that has been traditionally used to treat many diseases across the world. Licorice (Gancao in Chinese) is the dried root and rhizome of G. glabra, G. uralensis, or G. inflata. Licorice plays an important role in traditional Chinese medicine (TCM), and is the most frequently used in Chinese herbal formulas.
Licorice root has been used for years to regulate gastrointestinal function in traditional Chinese medicine. Glycyrrhizin, glycyrrhizinic acid, isoliquiritin, and glycyrrhizic acid are other main chemicals in this plant with anti-atherogenic, anti-cancer, anti-diabetic, anti-microbial, antispasmodic, anti-inflammatory, and anti-asthmatic properties. Licorice has also been documented to help with weariness and debilitation in China. In addition, licorice acts as an anti-inflammatory, reducing allergic responses and preventing liver damage. According to the World Health Organization, licorice is used as a demulcent for sore throats and an expectorant for bronchial catarrh and coughs.
2.2 Other Traditional Systems
Licorice, also known as the roots and stolen parts of Glycyrrhiza glabra L., is a Traditional Chinese Medicine (TCM) plant native to Central and South-Western Asia, Central Asia, and the Mediterranean region, with many pharmacological benefits including anti-viral, anti-cancer, anti-diabetic, anti-microbial, anti-malarial, and anti-inflammatory properties. The stem parts of the plant were traditionally used as a treatment for tuberculosis. Isoliquiritigenin is one of the constituents that the broader licorice tradition drew upon, though historical use was typically of whole-root preparations rather than the isolated compound.
3. Key Constituents, Chemical Context, and Mechanisms of Action
3.1 Relationship to Other Licorice Flavonoids
ISL is one of several bioactive chalcones and flavonoids in licorice root. Isoliquiritigenin, the precursor chalcone of liquiritigenin, demonstrated significant estrogenic activities, while liquiritigenin showed ERβ selectivity in competitive binding assays and isoliquiritigenin was equipotent for ER subtypes. The estrogenic activity of isoliquiritigenin could be the result of its cyclization to liquiritigenin under physiological conditions. This structural interconversion is pharmacologically significant, as it means the in vivo activity profile of ISL may partly reflect that of its metabolite.
3.2 Anti-Inflammatory Mechanisms
ISL elicits its anti-inflammatory activity by mediating various cellular processes. It inhibits the upstream of the nuclear factor kappa B (NF-κB) pathway and activates the nuclear factor erythroid related factor 2 (Nrf2) pathway. In cell studies, ISL inhibited reactive oxygen species (ROS) generation and cytotoxicity induced by t-BHP, and pro-inflammatory enzyme production induced by LPS in RAW 264.7 macrophages. Such cytoprotective effects coincided with the induction of AMP-activated protein kinase (AMPK)/Nrf2/antioxidant response element (ARE) signaling and the suppression of the NLRP3 and NF-κB pathways.
In LPS-stimulated bovine mammary epithelial cells (MAC-T), ISL treatment at 2.5, 5, and 10 μg/mL significantly reduced the mRNA and protein expression of cyclooxygenase-2 and inducible nitric oxide synthase (P < 0.01), and of the inflammatory cytokines interleukin-6 (P < 0.05), interleukin-1β (P < 0.01), and tumor necrosis factor-α (P < 0.01). Western blotting and immunofluorescence tests indicated that the phosphorylation levels of NF-κB p65 and the inhibitor of NF-κB were significantly decreased by ISL treatment, blocking the nuclear transfer of NF-κB p65.
3.3 Antioxidant Mechanisms
ISL increases antioxidant ability and decreases inflammation and cell apoptosis through activating the PGC-1α/Nrf2 pathway. ISL also phosphorylates MAPKs and upregulates Keap1, which induces the separation of Nrf2 from Keap1, activation of Nrf2 signaling, and enhancement of detoxification phase II enzyme activity. ISL activates SIRT1 to promote the Nrf2 antioxidant signaling pathway. ISL can inhibit GSK-3β activity by phosphorylation to enhance the Nrf2-related antioxidant gene expression and inhibit the NF-κB-induced inflammatory gene.
3.4 Anticancer Mechanisms
ISL demonstrates potent anticancer effects by: (1) inducing apoptosis and autophagy via mechanistic target of rapamycin (mTOR) inhibition and disruption of arachidonic acid pathways; (2) modulating microRNAs (e.g., miR-374a, miR-200c) to suppress epithelial-mesenchymal transition (EMT); (3) altering hormone receptor expression and inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mTOR signaling; and (4) reducing angiogenesis (VEGF/HIF-1α suppression) and inflammation (COX-2/NF-κB inhibition). ISL activates c-Jun N-terminal Kinase (JNK) and p38 MAPK while suppressing ERK, STAT3, and NF-κB pathways, ultimately triggering mitochondria-dependent apoptosis. The apoptotic effect of ISL can be reversed by the ROS scavenger N-acetylcysteine (NAC), underscoring the central role of oxidative stress in its mechanism of action.
3.5 Estrogenic Mechanisms
Licorice root contains chemically diverse compounds that exhibit estrogenic effects in vitro and in vivo. The chalcone isoliquiritigenin (ISL) is a component of licorice extract exhibiting either antitumorigenic activity or estrogen receptor (ER) alpha-dependent growth-promoting effects on breast cancer cells. Low levels of ISL have shown estrogenic and anti-proliferative activities in breast cancer cells, and ISL has been demonstrated to be a selective estrogen receptor beta agonist. ISL has low binding affinity for estrogen receptors (ERs), but potency and efficacy studies in stimulating the expression of estrogen-regulated genes reveal that ISL is an estrogen agonist. Of note, the potencies of the most active components are several orders of magnitude less than that of estradiol and other pharmaceutical estrogens used in hormone replacement therapies.
3.6 Neurological Mechanisms
ISL has been examined for its potential to inhibit human monoamine oxidase (hMAO) in vitro. ILG showed competitive inhibition of hMAO-A and mixed inhibition of hMAO-B with IC₅₀ values of 0.68 and 0.33 µM, respectively. Since ILG has been reported to reduce dopaminergic neurodegeneration and psychostimulant-induced toxicity (both of which are related to dopamine and vasopressin receptors), it has been investigated for binding affinity and modulatory functions on dopamine and vasopressin receptors; ILG was explored as an antagonist of the D1 receptor and an agonist of the D3 and V1A receptors with good potency.
Isoliquiritigenin has been studied for its activity as a tyrosinase inhibitor, NMDA receptor antagonist, GABA modulator, and for its potential antineoplastic and geroprotective effects. Despite its low expression in the brain due to high polarity, ISL can traverse the blood-brain barrier and exhibit neuroprotective effects in male MCAO-induced focal cerebral ischemic injury.
3.7 Renal Mechanisms
Isoliquiritigenin was found to attenuate renal tubular injury and renal dysfunction by inhibiting nuclear translocation of NF-κB and thus preventing inflammatory response. As a monomeric component of licorice flavonoids, ISL inhibits tumor necrosis factor-α (TNF-α)-induced reactive oxygen species (ROS) generation in epithelial cells, prevents the TNF-α-induced accumulation of vascular cell adhesion molecule (VCAM-1) and E-selectin, and attenuates excessive inflammatory responses. ISL also holds antiplatelet aggregation effects similar to aspirin, inhibits cyclooxygenase, and reduces thromboxane A2.
4. Scientific Evidence by Area of Use
Important note on evidence quality: Much of the scientific understanding of isoliquiritigenin stems from laboratory and animal studies. While these preclinical investigations demonstrate promising biological activities, large-scale human clinical trials are limited. The sections below make explicit the level of evidence available for each area.
4.1 Anti-Inflammatory Activity
Evidence level: Preclinical (in vitro and animal models); no registered human clinical trials identified in the peer-reviewed literature.
Isoliquiritigenin (ISL) is a bioactive chalcone compound isolated from licorice that has attracted increasing attention due to its excellent anti-inflammatory activity. In a study examining acute lung injury (ALI), ISL treatment significantly alleviated lung injury in LPS-induced ALI mice, reflected by reductions in histopathological changes, pulmonary edema, and protein leakage. ISL notably activated AMPK/Nrf2/ARE signaling and inhibited LPS-induced NLRP3 and NF-κB activation in the lung. Mechanistically, the repression of the NLRP3 and NF-κB pathways by ISL was found to be Nrf2-dependent and Nrf2-independent, respectively.
In a study of intracerebral hemorrhage, ISL, a flavonoid with a chalcone structure, was studied for its ability to activate Nrf2-mediated antioxidant systems and negatively regulate NF-κB and NLRP3 inflammasome pathways in ICH pathology. The ICH model was induced in male Sprague-Dawley rats, and different doses of ILG (10, 20, or 40 mg/kg) were administered intraperitoneally at 30 min, 12 h, 24 h, and 48 h after modeling.
4.2 Antioxidant Activity
Evidence level: Preclinical (in vitro and animal models).
ISL exhibits a diverse range of pharmacological activities, including antioxidant, anticancer, and anti-tumor properties. Notably, its robust antioxidant activity has garnered significant attention. Its antioxidant action is largely mediated through Nrf2 pathway activation, resulting in the upregulation of downstream antioxidant genes such as heme oxygenase-1 (HO-1), NQO-1, and superoxide dismutase. These findings are from cell and animal studies; human data are not available.
4.3 Anticancer Activity
Evidence level: Preclinical (in vitro and animal models); no human clinical trials identified.
ISL, a bioactive chalcone derived from Glycyrrhiza species, has shown promise in preclinical studies for its multifaceted anticancer properties, including modulation of metastatic processes. A 2025 systematic review evaluated preclinical evidence on ISL's mechanisms in breast cancer prevention and metastasis suppression, following PRISMA guidelines across PubMed/Medline, Scopus, Embase, and grey literature up to May 2025. Nanoparticle delivery systems (e.g., iRGD-targeted nanoparticles) have been explored to enhance ISL's tumor targeting and efficacy while maintaining low toxicity. Preclinical evidence highlights ISL's potential as a multi-target agent against breast cancer progression and metastasis.
ISL possesses significant anticancer activity against several types of cancers via inhibition of cell proliferation, induction of apoptosis, and/or prevention of metastasis. ISL also enhanced the chemosensitivity of multidrug-resistant human uterine sarcoma cancer cells (MES-SA/Dx5, MES-SA/Dx5-R) to doxorubicin.
A 2025 review focused on digestive system cancers, noting ISL also enhances the radiosensitivity of hepatocellular carcinoma (HCC) cells by modulating oxidative stress pathways. All findings in this domain are derived from cell lines and rodent tumor models.
4.4 Cardiovascular and Cardioprotective Activity
Evidence level: Preclinical (in vitro and animal models).
Inflammation and oxidative stress play essential roles in the occurrence and progression of diabetic cardiomyopathy (DCM). ISL, a natural chalcone, exhibits strong anti-inflammatory and antioxidant activities. In a study to investigate the protective effects of ISL on DCM, embryonic rat heart-derived H9c2 cells challenged with high concentrations of glucose were used to evaluate the anti-inflammatory and antioxidant effects of ISL. STZ-induced diabetic mice were used to study the effects of ISL in DCM in vivo. ISL effectively inhibited high glucose-induced hypertrophy, fibrosis, and apoptosis, probably by alleviating the inflammatory response and oxidative stress in H9c2 cells. Activation of Nrf2 by ISL can decrease infarct size and enhance cardiac function in myocardial ischemia-reperfusion injury, underscoring its therapeutic promise in cardiovascular pathologies.
4.5 Neuroprotective Activity
Evidence level: Preclinical (in vitro and animal models).
Multiple studies have explored the promising effects of ILG as a neuroprotective and neuro-rescuing compound through inhibition of intracellular ROS generation, antioxidative action, attenuation of synaptic dysfunction, neuronal damage, and neuroinflammation, confirming its usefulness in neurodegenerative disease models. ISL has been demonstrated to exert neuroprotective effects through activation of the Nrf2/NQO-1 signaling pathway, significantly attenuating neuroinflammation and ameliorating neurological deficits in Parkinson's disease models. Furthermore, ISL has been shown to inhibit microglia-mediated neuroinflammation in Parkinson's disease models, potentially through modulation of the JNK/NF-κB/AKT signaling cascade. It is under preliminary research for potential therapeutic effects against age-related neurodegenerative diseases by targeting multiple pathological mechanisms such as oxidative stress, neurotransmitter imbalance, and mitochondrial dysfunction.
4.6 Hepatoprotective Activity
Evidence level: Preclinical (in vitro and animal models).
In a rat model of acute liver injury induced by CCl₄, ISL held protective effects on liver injury in rats, and the mechanism was related to scavenging free radicals and anti-lipid peroxidation in liver tissue. Hepatoprotective effects are consistently associated in the literature with ISL's capacity to suppress oxidative stress and inflammatory signaling in hepatocytes, but human trial data are absent.
4.7 Antidiabetic and Renal Protective Activity
Evidence level: Preclinical (animal models).
Long-term administration of ISL could ameliorate excessive oxidative stress, downregulate the expression levels of renal fibrosis- and inflammation-related factors, and inhibit the JAK2/STAT3 signaling pathway. At all three dosages studied, ISL could efficiently improve the renal injury induced by streptozotocin (STZ) via ameliorating renal fibrosis, oxidative stress, and inhibiting JAK2/STAT3 signaling pathways in diabetic nephropathy (DN) rats.
4.8 Gastrointestinal Effects
Evidence level: Preclinical (in vitro and animal models).
In vivo, isoliquiritigenin produced a dual dose-related effect on charcoal meal transit, inhibitory at low doses and prokinetic at high doses. In vitro, isoliquiritigenin showed an atropine-sensitive concentration-dependent spasmogenic effect in isolated rat stomach fundus. A spasmolytic effect was observed in isolated rabbit jejunums, guinea pig ileums, and atropinized rat stomach fundus — indicating a calcium antagonist mechanism. In spite of low bioavailability, the gastroprotective effect of isoliquiritigenin was attributed to its high distribution in the stomach. Isoliquiritigenin prevented the occurrence of gastric ulcers by indomethacin, which is associated with increased gastric mucous secretion, presumably counteracting the decreased cyclooxygenase 2 induced by indomethacin.
4.9 Estrogenic and Reproductive Effects
Evidence level: Preclinical (in vitro cell studies and animal models); no human clinical trials identified.
Isoliquiritigenin is classified as a botanical estrogen used as a dietary supplement. One study investigated the efficacy of the commercially available botanical estrogenic compound ISL to alter performance on an operant working memory task (delayed spatial alternation, DSA). ISL is a compound found in licorice root that has been shown to have a wide range of effects on different biological systems, including estrogenic properties. This botanical is currently used in over-the-counter dietary supplements. Middle-aged (12-month old) Long-Evans female rats were ovariectomized and orally dosed with either 0, 6, 12, or 24 mg of ISL 60 minutes before testing.
Because these botanical estrogens behave as selective estrogen receptor modulators (SERMs), they likely can induce distinct conformations of the estrogen receptors (ERs) that recruit different sets of coregulators to generate distinct receptor multicomponent complexes, as observed for other SERMs such as tamoxifen and raloxifene.
4.10 Respiratory Effects
Evidence level: Preclinical (animal models).
Isoliquiritigenin exhibits powerful anti-inflammatory and antioxidant properties relevant to chronic obstructive pulmonary disease (COPD). Research on cigarette smoke-induced COPD in mice revealed that isoliquiritigenin reduced pulmonary inflammation by neutralizing free radicals and enhancing antioxidant enzyme expression.
4.11 Monoamine Oxidase Inhibition (Neuropsychiatric)
Evidence level: In vitro enzyme kinetics study.
In a study isolating liquiritigenin and isoliquiritigenin from Sinofranchetia chinensis to study inhibition of rat MAO A and B, both compounds were found to be inhibitory against both MAO A and B in a dose-dependent manner. IC₅₀ values of isoliquiritigenin were 13.9 µmol/L for MAO A inhibition and 47.2 µmol/L for MAO B inhibition. A follow-up study using human MAO found that ILG showed competitive inhibition of hMAO-A and mixed inhibition of hMAO-B with IC₅₀ values of 0.68 and 0.33 µM, respectively. These findings are entirely in vitro and have not been translated to human pharmacology studies.
5. Pharmacokinetics
5.1 Absorption and Bioavailability
Orally administered isoliquiritigenin can be rapidly absorbed by mice, whereas the absolute bioavailability was rather low at 11.8%. The low bioavailability of isoliquiritigenin is mainly caused by its rapid breakdown; the half-life of orally administered isoliquiritigenin is 4.6 hours, indicating that it is quickly metabolized and eliminated. The absorbed fraction of isoliquiritigenin was high, but the absolute bioavailability was low mainly due to its metabolism. Although ISL has been globally recognized for its health benefits, its oral administration is still restricted by sparing water solubility, poor bioavailability, and slow dissolution in the intestine.
5.2 Distribution and Metabolism
Isoliquiritigenin exhibits various biological activities but has low oral bioavailability (11.8%) in rats due to extensive metabolism in the liver and small intestine, resulting in high levels of its metabolites M1 and M2. Despite low bioavailability, the gastroprotective effect of isoliquiritigenin was attributed to its high distribution in the stomach. A key metabolic relationship is that ISL can be cyclized to its flavanone isomer liquiritigenin under physiological conditions, which affects its pharmacodynamics.
5.3 Novel Delivery Systems
Several approaches, including self-nanoemulsifying drug delivery systems (SNEDDS) and nanoparticles, are being explored to address the challenge of limited oral absorption and bioavailability associated with ISL. Nanoparticle delivery systems (e.g., iRGD-targeted nanoparticles) have been found to enhance ISL's tumor targeting and efficacy while maintaining low toxicity.
6. Dosages Reported in Studies
All dosages below are as reported in individual preclinical studies; no established human therapeutic doses are available from clinical trials.
- In an intracerebral hemorrhage rat model: different doses of ILG (10, 20, or 40 mg/kg) were administered intraperitoneally at 30 min, 12 h, 24 h, and 48 h after modeling.
- In a rat pharmacokinetics study: ISL was injected intravenously at a single dose of 10, 20, and 50 mg/kg, and administered orally at a single dose of 20, 50, and 100 mg/kg.
- In an ovariectomized rat working memory study: middle-aged (12-month old) Long-Evans female rats were orally dosed with either 0 mg, 6 mg, 12 mg, or 24 mg of ISL 60 minutes before testing.
- In an in vitro bovine mammary cell inflammation study: ISL treatment concentrations of 2.5, 5, and 10 μg/mL were used.
- It is estimated that the average daily exposure to ISL for humans ranges from 1–2 mg/kg through dietary sources.
7. Safety Considerations
7.1 Developmental Toxicity
Studies employing zebrafish embryos to study the developmental toxicity effect of ISL showed that ISL exposure instigated severe developmental toxicity in heart, liver, and nervous system over 4–96 hours post fertilization. Mortality and morphological abnormalities were also observed. High concentrations of ISL exposure resulted in abnormal phenotypes and embryonic malformations including pericardial edema, swim bladder defects, yolk retention, and curved body. ISL induces developmental toxicity and oxidative stress-induced apoptosis in zebrafish embryos and larvae through the Nrf2-HO1/JNK-ERK/mitochondrial pathway. These findings are from animal/zebrafish models; their relevance to human developmental exposure is not established, but they represent a known safety signal requiring further study.
7.2 Hepatotoxicity at High Doses
ISL, while exhibiting antioxidant, anticancer, anti-inflammatory, and anti-allergic properties, has been detected in both environmental and human samples. Previous studies have demonstrated that ISL exposure can lead to developmental deformities and aberrant immune responses. A study aimed to elucidate the effects of ISL exposure on endoplasmic reticulum (ER) stress in zebrafish embryos by assessing the expression levels of ER stress markers HSPA5 and CHOP, along with associated apoptosis factors. These hepatotoxic signals emerged at experimental (high) concentrations; the relationship to doses encountered in dietary supplements is not established.
7.3 Reproductive and Ovarian Effects
Phytoestrogens are phenolic compounds found in plants that can interact with estrogen receptors and other targets in endogenous estrogen production and action. Although potential benefits have been identified with the use of phytoestrogens, their adverse effects are less understood. The effect of ISL in embryonic development has not been fully elucidated, and the mechanisms underlying its target-organ toxicity and harmful side effects are still unclear.
7.4 General Target-Organ Toxicity
Further research is required to confirm target-organ toxicity or side-effect investigations for ISL. Isoliquiritigenin has been studied for its potential pharmacological properties, and ongoing research is exploring its use in food additives and therapeutic applications, although further studies are needed to evaluate its safety and potential target-organ toxicity.
7.5 Estrogenic Activity and Hormone-Sensitive Conditions
The chalcone isoliquiritigenin (ISL) is a component of licorice extract exhibiting either antitumorigenic activity or estrogen receptor (ER) alpha-dependent growth-promoting effects on breast cancer cells. This apparent duality — where ISL can act as a phytoestrogen at one concentration while showing anti-proliferative activity at another — represents an unresolved complexity of relevance to individuals with hormone-sensitive conditions. These data demonstrated that Glycyrrhiza species with different contents of liquiritigenin have various levels of estrogenic activities, suggesting the importance of precise labeling of botanical supplements.
7.6 Potential Drug Interactions
Because ISL inhibits both MAO-A and MAO-B in vitro, there is a theoretical basis to consider interactions with drugs metabolized by these enzymes or with monoaminergic drugs, though this has not been studied in humans. ISL holds antiplatelet aggregation effects similar to aspirin and inhibits cyclooxygenase, suggesting a potential for additive effects with anticoagulant or antiplatelet medications — though this has not been examined in human pharmacological studies. The low oral bioavailability of ISL may mitigate some of these theoretical concerns, but the absence of human data means interactions cannot be systematically excluded.
7.7 Consumer Exposure Context
Due to the widespread promotion of isoliquiritigenin, many individuals consume isoliquiritigenin-containing foods, as well as different Chinese herbs, every day. The excessive consumption of isoliquiritigenin-containing products, such as candy, tobacco, and dietary supplements, results in the accumulation of isoliquiritigenin in the human body.
8. Summary of Evidence Landscape
The practical application of ISL on the various disease prevention and treatments may stem from its numerous pharmacological properties such as anti-inflammatory, anti-microbial, anti-oxidative, anticancer activities, immunoregulatory, hepatoprotective, and cardioprotective effects. However, the evidence base for ISL remains predominantly preclinical. A 2025 systematic review evaluated exclusively preclinical evidence on ISL's mechanisms in breast cancer prevention and metastasis suppression, illustrating that even the most comprehensive reviews of ISL's cancer biology are based on cell and animal data. The compound's oral administration is still restricted by sparing water solubility, poor bioavailability, and slow dissolution in the intestine, which represents a significant translational hurdle. Researchers have consistently called for further human clinical trials before any therapeutic claims can be substantiated.
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