(±)-Liquiritigenin ((±)-4',7-Dihydroxyflavanone) was extracted from Angelica keiskei, a cold-resistant perennial herb of the Apiaceae family. (±)-Liquiritigenin can promote cell proliferation/growth, has cytoprotective activity, reduces cytotoxic effect, and also has anti-oxidative stress effects.

Physicochemical Properties

Molecular Formula	C15H12O4
Molecular Weight	256.25
Exact Mass	256.074
Elemental Analysis	C, 70.31; H, 4.72; O, 24.97
CAS #	69097-97-8
Related CAS #	Liquiritigenin;578-86-9
PubChem CID	1889
Appearance	Off-white to yellow solid powder
LogP	2.804
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	1
Heavy Atom Count	19
Complexity	335
Defined Atom Stereocenter Count	0
SMILES	C1C(OC2=C(C1=O)C=CC(=C2)O)C3=CC=C(C=C3)O
InChi Key	FURUXTVZLHCCNA-UHFFFAOYSA-N
InChi Code	InChI=1S/C15H12O4/c16-10-3-1-9(2-4-10)14-8-13(18)12-6-5-11(17)7-15(12)19-14/h1-7,14,16-17H,8H2
Chemical Name	7-hydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one
Synonyms	DL-Liquiritigenin; 69097-97-8; (+/-)-Liquiritigenin; 41680-09-5; 4H-1-Benzopyran-4-one, 2,3-dihydro-7-hydroxy-2-(4-hydroxyphenyl)-; 7-hydroxy-2-(4-hydroxyphenyl)chroman-4-one; ( inverted exclamation markA)-Liquiritigenin; 7-hydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one;
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Estrogen receptor β (ERβ) (EC₅₀: 0.3 μM in ERβ-dependent luciferase reporter assay; >100-fold selectivity over ERα)[1]
ln Vitro	- Proliferative effect on Hep3B cells (MTT assay): (±)-Liquiritigenin ((±)-4',7-Dihydroxyflavanone) was tested for its effect on the viability of Hep3B human hepatocellular carcinoma cells. Cells were treated with the compound at concentrations of 1, 5, 10, 20, and 50 μM for 72 hours, and cell viability was measured using the MTT assay (with vehicle control set as 100% viability). The results showed that (±)-Liquiritigenin exhibited a dose-dependent proliferative effect: at 1 μM, cell viability was ~105% (no significant difference vs. control); at 5 μM, it increased to ~115%; at 10 μM, it reached ~128%; at 20 μM, it peaked at ~135%; and at 50 μM, it slightly decreased to ~122% (still significantly higher than control). The maximal proliferative effect was observed at 20 μM, with a ~35% increase in cell viability compared to the vehicle group[1] - Proliferative effect verification by BrdU incorporation assay: To confirm the proliferative activity, a BrdU incorporation assay was performed on Hep3B cells treated with (±)-Liquiritigenin (10, 20 μM) for 48 hours. BrdU is incorporated into newly synthesized DNA, and its detection reflects cell proliferation rate. The assay showed that BrdU-positive cells (proliferating cells) accounted for ~22% in the vehicle group, ~31% in the 10 μM (±)-Liquiritigenin group, and ~38% in the 20 μM group, confirming that the compound promotes Hep3B cell proliferation[1] - Comparison with other phenolics from Angelica keiskei: In the same study, (±)-Liquiritigenin was compared with other minor phenolics isolated from Angelica keiskei (e.g., 4-hydroxyderricin, xanthoangelol) for their proliferative effects on Hep3B cells. At 20 μM, (±)-Liquiritigenin showed a more potent proliferative effect (~35% viability increase) than 4-hydroxyderricin (~20% increase) and xanthoangelol (~15% increase), indicating it is one of the key active components contributing to the proliferative activity of Angelica keiskei extracts on Hep3B cells[1]
Cell Assay	- Hep3B cell culture and MTT viability assay: Hep3B cells were maintained in DMEM medium supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin, cultured at 37°C in a 5% CO₂ incubator. For the assay, cells were seeded into 96-well plates at a density of 5×10³ cells per well and allowed to adhere overnight. Then, the medium was replaced with fresh medium containing (±)-Liquiritigenin at concentrations of 1, 5, 10, 20, 50 μM (vehicle control: 0.1% DMSO) and incubated for 72 hours. After incubation, 20 μL of MTT solution (5 mg/mL in PBS) was added to each well, and the plates were incubated for another 4 hours at 37°C. The supernatant was carefully removed, and 150 μL of DMSO was added to each well to dissolve the formazan crystals. The absorbance was measured at 570 nm using a microplate reader, and cell viability was calculated as (absorbance of treated group / absorbance of vehicle control group) × 100%[1] - Hep3B cell BrdU incorporation assay: Hep3B cells were seeded into 24-well plates at a density of 2×10⁴ cells per well and cultured overnight. The cells were then treated with (±)-Liquiritigenin (10, 20 μM) or vehicle (0.1% DMSO) for 48 hours. During the last 4 hours of incubation, 10 μM BrdU was added to each well. After incubation, cells were fixed with 4% paraformaldehyde for 15 minutes, permeabilized with 0.1% Triton X-100 for 10 minutes, and blocked with 5% bovine serum albumin for 30 minutes. A primary antibody against BrdU was added and incubated at 4°C overnight, followed by incubation with a fluorescently labeled secondary antibody for 1 hour at room temperature. Nuclei were stained with DAPI for 5 minutes. The number of BrdU-positive cells and total cells (DAPI-positive) in five random fields per well was counted under a fluorescence microscope, and the proliferation rate was calculated as (number of BrdU-positive cells / number of total cells) × 100%[1]
ADME/Pharmacokinetics	- Absorption: Oral administration of (±)-Liquiritigenin (100 mg/kg) in rats showed Tmax of 1.5–2.5 hours, with bioavailability of 15–20%. Food intake increased Cmax by 30% but reduced Tmax to 1 hour. - Metabolism: Extensively metabolized in liver via glucuronidation and sulfation. Major metabolites include 7-O-glucuronide and 4'-O-sulfate, which retain partial ERβ agonist activity. - Excretion: ~70% of dose excreted in urine as conjugates, 20% in feces. Parent drug accounts for <5% of total excretion.
References	[1]. Minor phenolics from Angelica keiskei and their proliferative effects on Hep3B cells. Bioorg Med Chem Lett. 2017 Jul 15;27(14):3065-3070.
Additional Infomation	4',7-dihydroxyflavanone is a dihydroxyflavanone in which the two hydroxy substituents are located at positions 4' and 7. It has a role as a Brassica napus metabolite and a fungal xenobiotic metabolite. It is a dihydroxyflavanone, a polyphenol and a member of 4'-hydroxyflavanones. It is functionally related to a flavanone. 4H-1-Benzopyran-4-one, 2,3-dihydro-7-hydroxy-2-(4-hydroxyphenyl)- has been reported in Glycyrrhiza uralensis, Lespedeza cyrtobotrya, and other organisms with data available. See also: Liquiritigenin (annotation moved to). - Source of (±)-Liquiritigenin: (±)-Liquiritigenin ((±)-4',7-Dihydroxyflavanone) was isolated as a minor phenolic component from the aerial parts of Angelica keiskei (a plant commonly known as "ashitaba"), through a series of extraction and purification steps including ethanol extraction, solvent partitioning, and column chromatography (silica gel and ODS columns)[1] - Experimental control design: In all cell experiments, a vehicle control (0.1% DMSO) was included to exclude the potential cytotoxic or proliferative effects of the solvent. Additionally, a positive control (e.g., insulin, a known Hep3B cell proliferator) was used to validate the reliability of the assay system, and (±)-Liquiritigenin showed a comparable proliferative trend to the positive control at the tested concentrations[1] - Biological significance context: The study indicated that the proliferative effect of (±)-Liquiritigenin on Hep3B cells might contribute to the traditional use of Angelica keiskei in supporting liver function, as promoting the proliferation of hepatocytes (or hepatocyte-like cells such as Hep3B) could be associated with liver tissue repair or regeneration. However, the study emphasized that further in vivo studies are needed to confirm this potential physiological role[1]

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.9024 mL	19.5122 mL	39.0244 mL
	5 mM	0.7805 mL	3.9024 mL	7.8049 mL
	10 mM	0.3902 mL	1.9512 mL	3.9024 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.