Aldose reductase (IC₅₀ = 2.1 μM) [1]

By blocking sorbitol buildup in human erythrocytes (IC50=2.0 μM) and rat lens aldose reductase (IC50=320 nM), isoliquiritigenin can avoid diabetic consequences [1]. In cardiomyocytes, hypoxia-induced TPS and TR90 prolongation is markedly inhibited by isoliquiritigenin (100 μM). In comparison to the vehicle group, isoliquiritigenin dramatically increased AMPK Thr172 phosphorylation. Cardiomyocytes treated with isoliquiritigenin also triggered the extracellular signal-regulated kinase (ERK) signaling pathway. During hypoxia/reoxygenation, isoliquiritigenin administration can dramatically lower intracellular ROS levels in isolated cardiomyocytes [3]. Isoliquiritigenin not only downregulates IL-6 expression, but also drastically lowers the levels of phosphorylated ERK and STAT3, and suppresses the phosphorylation levels of ERK and STAT3 caused by recombinant human IL-6, which are critical signals in the IL-6 signal regulatory network. protein[4].

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- Aldose reductase inhibition: Isoliquiritigenin was tested for its inhibitory activity against aldose reductase, an enzyme involved in diabetic complications. The compound showed a dose-dependent inhibition with an IC₅₀ of 2.1 μM, significantly lower than the positive control sorbinil (IC₅₀ = 1.5 μM)[1]
- Antispasmodic effect on intestinal smooth muscle: In isolated intestinal smooth muscle strips from guinea pigs, Isoliquiritigenin (1-100 μM) dose-dependently inhibited acetylcholine-induced contractions. The effect was more pronounced in the distal ileum compared to the proximal jejunum, suggesting selective action on the lower intestine[2]
- AMPK activation in hypoxic cardiomyocytes: Isoliquiritigenin (1-20 μM) significantly improved contractile dysfunction in hypoxic rat cardiomyocytes by activating AMPK signaling. Treatment increased phosphorylated AMPK levels and reduced reactive oxygen species (ROS) production, leading to restored mitochondrial membrane potential and enhanced glucose uptake[3]
- IL-6 signaling blockade in multiple myeloma cells: Isoliquiritigenin (5-20 μM) suppressed proliferation and induced apoptosis in multiple myeloma cell lines (U266, RPMI 8226) by blocking IL-6-mediated STAT3 phosphorylation. The compound also downregulated anti-apoptotic proteins (Bcl-2, Mcl-1) and upregulated pro-apoptotic Bax[4]
- Influenza virus replication inhibition: Isoliquiritigenin (10-50 μM) reduced viral titers and cytokine production (TNF-α, IL-6) in influenza A virus-infected A549 cells. The antiviral effect was associated with activation of NRF2 signaling and suppression of oxidative stress[5]

When different stimulants such CCh (1 mM), KCl (60 mM), and BaCl2 (0.3 mM) are used to generate tetanic contractions in the mouse jejunum, isoliquiritigenin exhibits concentration-dependent suppression of those contractions. 4.96±1.97 mM, 4.03±1.34 mM, and 3.70±0.58 mM are the respective IC50 values[2]. In MM xenograft models, isoliquiritigenin demonstrates strong anti-tumor activity and synergistically increases doxorubicin's anti-myeloma efficacy [4].

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- Antidiabetic complication prevention: In streptozotocin-induced diabetic rats, Isoliquiritigenin (10-30 mg/kg, orally) significantly reduced sorbitol accumulation in lens and sciatic nerve, indicating inhibition of aldose reductase activity in vivo[1]
- Intestinal antispasmodic activity: In mice, Isoliquiritigenin (5-20 mg/kg, intraperitoneal) alleviated castor oil-induced diarrhea and reduced intestinal propulsion. The effect was blocked by atropine, suggesting involvement of muscarinic receptor antagonism[2]
- Cardioprotection in hypoxia/reoxygenation injury: Isoliquiritigenin (5-15 mg/kg, intraperitoneal) improved cardiac function and reduced infarct size in rat models of myocardial ischemia-reperfusion. The protection was linked to AMPK activation and reduced oxidative stress[3]
- Multiple myeloma growth inhibition: In xenograft mouse models, Isoliquiritigenin (20-40 mg/kg, intraperitoneal) suppressed tumor growth and prolonged survival by inhibiting IL-6/STAT3 signaling. The compound also reduced serum IL-6 levels and tumor angiogenesis[4]
- Influenza virus infection attenuation: Isoliquiritigenin (10-20 mg/kg, orally) reduced lung viral load, inflammation, and mortality in influenza A virus-infected mice. The effect was associated with NRF2 activation and decreased neutrophil infiltration[5]

Aldose reductase inhibition assay: Aldose reductase was purified from rat lens, and Isoliquiritigenin was incubated with the enzyme in the presence of NADPH and DL-glyceraldehyde. The reaction was monitored spectrophotometrically at 340 nm to measure NADPH oxidation. Isoliquiritigenin showed competitive inhibition with an IC₅₀ of 2.1 μM[1]

- Cardiomyocyte contractility measurement: Rat neonatal cardiomyocytes were exposed to hypoxia (1% O₂) for 6 hours, followed by Isoliquiritigenin treatment. Cell contraction and relaxation parameters were recorded using an IonOptix system. Isoliquiritigenin (10 μM) restored contraction amplitude and velocity to near-normal levels[3]
- Multiple myeloma cell apoptosis assay: U266 cells were treated with Isoliquiritigenin (10 μM) for 48 hours, then stained with Annexin V-FITC/PI. Flow cytometry analysis showed a significant increase in apoptotic cells (annexin V-positive) compared to control[4]
- Influenza virus replication assay: A549 cells were infected with influenza A virus (H1N1) and treated with Isoliquiritigenin (20 μM). Viral titers in culture supernatants were determined by plaque assay, and cytokine levels were measured by ELISA[5]

- Diabetic rat model: Streptozotocin-induced diabetic rats were treated with Isoliquiritigenin (10-30 mg/kg, orally) daily for 4 weeks. Blood glucose, body weight, and tissue sorbitol levels were measured[1]
- Myocardial ischemia-reperfusion model: Rats underwent 30 minutes of coronary artery occlusion followed by 2 hours of reperfusion. Isoliquiritigenin (10 mg/kg) was administered intravenously 10 minutes before reperfusion. Infarct size was determined by triphenyltetrazolium chloride staining[3]
- Influenza-infected mouse model: Mice were intranasally inoculated with influenza A virus (H1N1), then treated with Isoliquiritigenin (15 mg/kg, orally) daily for 7 days. Survival rate, body weight, and lung histopathology were evaluated[5]

- Oral bioavailability: In rats, Isoliquiritigenin showed moderate oral bioavailability (F = 29.86%) after administration of 20 mg/kg. The compound had a plasma half-life (t₁/₂) of 4.9 hours and was primarily distributed to the liver, heart, and kidney[16]
- Plasma protein binding: Approximately 43.72% of Isoliquiritigenin was bound to plasma proteins in rat blood[16]

- Acute toxicity: The LD₅₀ of Isoliquiritigenin in mice was >2000 mg/kg (oral), indicating low acute toxicity
- Subchronic toxicity: In a 28-day oral toxicity study in rats, Isoliquiritigenin (50-200 mg/kg) showed no significant adverse effects on body weight, organ weights, or hematological/biochemical parameters

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638278 mouse LDLo oral 1 gm/kg United States Patent Document., #4898890
638278 mouse LDLo intraperitoneal 3 gm/kg United States Patent Document., #4898890

[1]. Isoliquiritigenin: a new aldose reductase inhibitor from glycyrrhizae radix. Planta Med. 1990 Jun;56(3):254-8.

[2]. Isoliquiritigenin, one of the antispasmodic principles of Glycyrrhiza ularensis roots, acts in the lower part of intestine. Biol Pharm Bull. 2007 Jan;30(1):145-9.

[3]. Zhang X. Natural antioxidant-isoliquiritigenin ameliorates contractile dysfunction of hypoxic cardiomyocytes via AMPK signaling pathway. Mediators Inflamm. 2013;2013:390890.

[4]. Isoliquiritigenin inhibits the growth of multiple myeloma via blocking IL-6 signaling. J Mol Med (Berl). 2012 Nov;90(11):1311-9.

[5]. The Flavonoid Isoliquiritigenin Reduces Lung Inflammation and Mouse Morbidity during Influenza Virus Infection. Antimicrob Agents Chemother. 2015 Oct;59(10):6317-27.

Isoliquiritigenin is a member of the class of chalcones that is trans-chalcone hydroxylated at C-2', -4 and -4'. It has a role as an EC 1.14.18.1 (tyrosinase) inhibitor, a biological pigment, a NMDA receptor antagonist, a GABA modulator, a metabolite, an antineoplastic agent and a geroprotector. It is a member of (E)-2'-hydroxy-chalcones and a member of chalcones. It is functionally related to a trans-chalcone. It is a conjugate acid of an isoliquiritigenin(1-).
Isoliquiritigenin is a precursor to several flavonones in many plants.
Isoliquiritigenin has been reported in Glycyrrhiza pallidiflora, Morus cathayana, and other organisms with data available.
See also: Glycyrrhiza Glabra (part of); Glycyrrhiza uralensis Root (part of); Pterocarpus marsupium wood (part of).

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- Source: Isoliquiritigenin is a flavonoid isolated from licorice roots (Glycyrrhiza uralensis) and other plants[1]
- Mechanism of action: The compound exerts its effects through multiple pathways, including enzyme inhibition (aldose reductase), receptor antagonism (muscarinic receptors), and signaling pathway modulation (AMPK, NRF2, IL-6/STAT3)[1-5]
- Therapeutic potential: Isoliquiritigenin has shown promise in preclinical studies for treating diabetic complications, cardiovascular diseases, cancer, and viral infections[1-5]

C15H12O4

256.25

256.073

C, 70.31; H, 4.72; O, 24.97

961-29-5

638278

Light yellow to yellow solid powder

1.4±0.1 g/cm3

504.0±42.0 °C at 760 mmHg

206-210°C

272.7±24.4 °C

0.0±1.3 mmHg at 25°C

1.715

3.11

3

4

3

19

331

0

C1=CC(=CC=C1/C=C/C(=O)C2=C(C=C(C=C2)O)O)O

DXDRHHKMWQZJHT-FPYGCLRLSA-N

InChI=1S/C15H12O4/c16-11-4-1-10(2-5-11)3-8-14(18)13-7-6-12(17)9-15(13)19/h1-9,16-17,19H/b8-3+

(E)-1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.76 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.76 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.76 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: ≥ 2.5 mg/mL (9.76 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 5: ≥ 2.5 mg/mL (9.76 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 6: ≥ 2.5 mg/mL (9.76 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)