Glycyrrhetinic acid

Names

[ CAS No. ]:
471-53-4

[ Name ]:
Glycyrrhetinic acid

[Synonym ]:
MFCD00003706
(3β)-3-Hydroxy-11-oxoolean-12-en-30-oic acid
Glycyrrhetinic acid
(2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bR)-10-Hydroxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydro-2-picenecarboxylic acid
18-beta-Glycyrrhetinic acid
Arthrodont
EINECS 207-444-6
18-β-Glycyrrhetinic Acid
glycyrrhetin
GM 1658
Uralenic acid
3β-Hydroxy-11-oxoolean-12-en-30-oic acid
18b-Glycyrrhetic acid
Biosone
Olean-12-en-30-oic acid, 3β-hydroxy-11-oxo-
18β-Glycyrrhetinic acid
STX 352
Glycyrrhetic Acid
PO 12
Olean-12-en-30-oic acid, 3-hydroxy-11-oxo-, (3β)-
3b-Hydroxy-11-oxoolean-12-en-30-oic Acid
18b-Glycyrrhetinic Acid
Glycyrrhetinate
(3b,20b)-3-Hydroxy-11-oxoolean-12-en-29-oic Acid
ENOLOXONE
enoxolone

Biological Activity

[Description]:

18β-Glycyrrhetinic acid is the major bioactive component of Glycyrrhizae Radix and possesses anti-ulcerative, anti-inflammatory and antiproliferative properties.

[Related Catalog]:

Research Areas >> Cancer

Research Areas >> Inflammation/Immunology

Natural Products >> Terpenoids and Glycosides

[Target]

Human Endogenous Metabolite

[In Vitro]

18β-Glycyrrhetinic acid is the major bioactive component of Glycyrrhizae Radix and possesses anti-ulcerative, anti-inflammatory and antiproliferative properties. MTS assay demonstrates that 24 h treatment of 18β-Glycyrrhetinic acid suppresses cell proliferation in both cell lines in a dose-dependent manner. 18β-Glycyrrhetinic acid at 160 μM significantly decreases the percentage of viable cells to around 40.5±10.5% in A549 and 38.3±4.6% in NCI-H460 (p<0.01 respectively). When the cells are treated with 320 μM 18β-Glycyrrhetinic acid, a greater inhibitory effects on cell proliferation is shown, as the percentage of viable cells is below 30% compare with untreated controls (p<0.001). Treatment with 18β-Glycyrrhetinic acid at 160 μM and 320 μM decreases the levels of full-length PARP and increases the levels of cleaved-PARP[1].

[In Vivo]

Rats in 18β-Glycyrrhetinic acid+Triptolide (TP) group which receive low-dose 18β-Glycyrrhetinic acid (50 mg/kg) have significant reductions in the three serum parameters when compare with TP rats. Rats in 18β-Glycyrrhetinic acid+TP group which receive the high-dose 18β-Glycyrrhetinic acid (100 mg/kg) have slightly lowered the levels of three liver enzymes, the reductions do not reach statistical significance compare with TP group. Contrastingly, preadministration of low-dose 18β-Glycyrrhetinic acid protects animals from TP-induced hepatic lesions. On the contrary, low-dose 18β-Glycyrrhetinic acid (50 mg/kg) markedly suppresses the release of the four cytokines above[3].

[Cell Assay]

Primary microglia cultures are used in this study. For treatment assay, microglia are incubated with complete DMEM and stimulated with or without 100 ng/mL IFN-γ in the presence or absence of 18β-Glycyrrhetinic acid (25 μM and 50 μM) at 37°C in a humidified incubator with 5% CO2. For cell migration assay, the isolated primary microglia that seeded in complete DMEM medium are stimulated with or without IFN-γ (100 ng/mL), and treated with different doses of 18β-Glycyrrhetinic acid, 24 h later, the microglia culture supernatants are collected and added to the lower chambers of Transwell inserts[2].

[Animal admin]

Healthy Wistar rats (male, 200±20 g) are used and divided into five groups with 10 individuals for each group randomly. Animals in normal control (NC) group receive distilled water for 6 days and 0.5% CMC-Na for the last 3 days. Rats in Triptolide model group (TP), 18β-Glycyrrhetinic acid low-dose group (GAL+TP), and 18β-Glycyrrhetinic acid high-dose group (GAH+TP) receive distilled water, 18β-Glycyrrhetinic acid (50 mg/kg, p.o., dissolved in distilled water), or 18β-Glycyrrhetinic acid (100 mg/kg, p.o., dissolved in distilled water) for consecutive 6 days, respectively, and liver injury is induced by TP (2.4 mg/kg, p.o., suspended in 0.5% CMC-Na) for the last 3 days. Animals in the above three groups receive TP 6 hours after distilled water or 18β-Glycyrrhetinic acid treatment on the last 3 days[3].

[References]

[1]. Huang RY, et al. 18β-Glycyrrhetinic acid suppresses cell proliferation through inhibiting thromboxane synthase in non-small cell lung cancer. PLoS One. 2014 Apr 2;9(4):e93690.

[2]. Zhou J, et al. 18β-glycyrrhetinic acid suppresses experimental autoimmune encephalomyelitis through inhibition of microglia activation and promotion of remyelination. Sci Rep. 2015 Sep 2;5:13713.

[3]. Yang G, et al. Protective Effect of 18β-Glycyrrhetinic Acid against Triptolide-Induced Hepatotoxicity in Rats. Evid Based Complement Alternat Med. 2017;2017:3470320.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
588.3±50.0 °C at 760 mmHg

[ Melting Point ]:
292 - 295ºC

[ Molecular Formula ]:
C₃₀H₄₆O₄

[ Molecular Weight ]:
470.684

[ Flash Point ]:
323.7±26.6 °C

[ Exact Mass ]:
470.339600

[ PSA ]:
74.60000

[ LogP ]:
6.57

[ Vapour Pressure ]:
0.0±3.7 mmHg at 25°C

[ Index of Refraction ]:
1.563

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: RK0180000

CHEMICAL NAME :: Olean-12-en-30-oic acid, 3-beta-hydroxy-11-oxo-

CAS REGISTRY NUMBER :: 471-53-4

BEILSTEIN REFERENCE NO. :: 2229654

LAST UPDATED :: 199701

DATA ITEMS CITED :: 3

MOLECULAR FORMULA :: C30-H46-O4

MOLECULAR WEIGHT :: 470.76

WISWESSER LINE NOTATION :: L F6 E6 B666 CV DUTJ A1 HVQ H1 K1 N1 O1 S1 S1 TQ -ALPHA

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 308 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,319,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 56 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: CSLNX* U.S. Army Armament Research & Development Command, Chemical Systems Laboratory, NIOSH Exchange Chemicals. (Aberdeen Proving Ground, MD 21010) Volume(issue)/page/year: NX#02067

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H319

[ Precautionary Statements ]:
P301 + P312 + P330-P305 + P351 + P338

[ Hazard Codes ]:
Xn: Harmful;

[ Risk Phrases ]:
R22;R36

[ Safety Phrases ]:
22-24/25

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
RK0180000

[ HS Code ]:
2938909030

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2918990090

[ Summary ]:
2918990090. other carboxylic acids with additional oxygen function and their anhydrides, halides, peroxides and peroxyacids; their halogenated, sulphonated, nitrated or nitrosated derivatives. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

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