Glycyrrhizic acid

Glycyrrhizic acid is a triterpenoid saponinl, acting as a direct HMGB1 antagonist, with anti-tumor, anti-diabetic activities.

Signaling Pathways >> Others >> Others

Research Areas >> Metabolic Disease

Natural Products >> Terpenoids and Glycosides

Research Areas >> Cancer

Glycyrrhizic acid shows a series of anti-cancer-related pharmacological activities, such as broad-spectrum anti-cancer ability, resistance to the tissue toxicity caused by chemotherapy and radiation, drug absorption enhancing effects and anti-multidrug resistance (MDR) mechanisms, as a carrier material in drug delivery systems[1]. In intestinal NCI-H716 cells that secretes GLP-1, Glycyrrhizic acid promotes GLP-1 secretion with a marked elevation of calcium levels. Glycyrrhizic acid can enhance GLP-1 secretion through TGR5 activation[2].

In type 1-like diabetic rats induced by streptozotocin (STZ-treated rats), Glycyrrhizic acid increases the level of plasma GLP-1, which is blocked by triamterene at a dose sufficient to inhibit Takeda G-protein-coupled receptor 5 (TGR5)[1]. Glycyrrhizic acid (Glycyrrhizic acid; 50 mg/kg, i.p.) significantly decreases the levels of TgAb, HMGB1, TNF-α, IL-6, IL-1β in mice[3].

Mice[3] NOD.H-2h4 mice are fed in the animal house until 4 weeks of age. A total of 24 male mice are then randomly separated into three different groups (n=8 per group). Mice in the control group are given sterile water without supplement. Mice in the iodine supplement (NaI) group are given 0.005% NaI in the drinking water. Mice in the NaI+Glycyrrhizic acid group are treated with 50 mg/kg Glycyrrhizic acid once daily for 4 weeks, administered via intraperitoneal injection after 8 weeks of iodine supplementation. Thyroid tissues are removed surgically under anesthesia, washed with cold saline, blotted on filter paper and weighed using an electronic balance. The thyroid gland tissues are then stored at -80°C until use[3].

[1]. Su X, et al. Glycyrrhizic acid: A promising carrier material for anticancer therapy. Biomed Pharmacother. 2017 Sep 5;95:670-678

[2]. Wang LY, et al. Glycyrrhizic acid increases glucagon like peptide-1 secretion via TGR5 activation in type 1-like diabetic rats. Biomed Pharmacother. 2017 Sep 4;95:599-604.

[3]. Li C, et al. Glycyrrhizin, a Direct HMGB1 Antagonist, Ameliorates Inflammatory Infiltration in a Model of Autoimmune Thyroiditis via Inhibition of TLR2-HMGB1 Signaling. Thyroid. 2017 May;27(5):722-731.

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DATA ITEMS CITED :

10

MOLECULAR FORMULA :

C42-H62-O16

MOLECULAR WEIGHT :

823.04

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

280 mg/kg/4W

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Nutritional and Gross Metabolic - changes in phosphorus

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

662 mg/kg/1Y-I

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - muscle weakness Nutritional and Gross Metabolic - changes in potassium

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>300 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

4320 mg/kg

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - respiratory stimulation Lungs, Thorax, or Respiration - other changes

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

589 mg/kg

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - respiratory stimulation Lungs, Thorax, or Respiration - other changes

MUTATION DATA

TYPE OF TEST :

Micronucleus test

TEST SYSTEM :

Rodent - hamster Ovary

DOSE/DURATION :

100 umol/L

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 367,99,1996