Glycyrrhizin
Glycyrrhizin Uses, Dosage, Side Effects, Food Interaction and all others data.
Glycyrrhizin is extracted from the root of the licorice plant; Glycyrrhiza glabra. It is a triterpene glycoside with glycyrrhetinic acid that possesses a wide range of pharmacological and biological activities. When extracted from the plant, it can be obtained in the form of ammonium glycyrrhizin and mono-ammonium glycyrrhizin. Glycyrrhizin has been developed in Japan and China as a hepatoprotective drug in cases of chronic hepatitis. From January 2014, glycyrrhizic acid as part of the licorice extract was approved by the FDA as an existing food sweetener. It was approved by Health Canada to be used in over-the-counter products but all the products are currently on the status canceled post marketed.
Glycyrrhizin was reported to present antiallergic, antiviral and anti-inflammatory activities as well as improvements in glucose tolerance.
The effect of glycyrrhizic acid in metabolic syndrome generates a significant decrease in blood glucose, fasting blood glucose and mean serum insulin concentration.
| Trade Name | Glycyrrhizin |
| Generic | Glycyrrhizic acid |
| Glycyrrhizic acid Other Names | 18-beta-Glycyrrhizic acid, Glizigen, Glycyrrhizin |
| Type | |
| Formula | C42H62O16 |
| Weight | Average: 822.942 Monoisotopic: 822.403785916 |
| Protein binding | Glycyrrhizic acid does not bind to any plasma proteins as it is not absorbed systemically. On the other hand, its main active metabolite, glycyrrhetinic acid presents a very large binding to serum proteins such as albumin. |
| Groups | Approved, Experimental |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Glycyrrhizin is widely applied in foods as a natural sweetener. As a therapeutic agent, is has been used in a vast variety of formulations as it is reported to be anti-inflammatory, anti-ulcer, anti-allergic, antioxidant, anti-tumor, anti-diabetic and hepatoprotective. Due to this properties, its indications have been: treatment of premenstrual syndrome, treatment of viral infections, anti-lipidemic and antihyperglycemic. It is also known to be used as a remedy for peptic ulcer and other stomach diseases.
Glycyrrhizin is also used to associated treatment for these conditions: Hyperglycemia, Premenstrual Syndrome
How Glycyrrhizin works
Glycyrrhizin can be found in the alpha and beta forms. The alpha form is predominant in the liver and duodenum and thus, it is thought that the anti-inflammatory liver effect of this drug are mainly due to the action of this isomer. Glycyrrhizin anti-inflammatory effect is generated via suppression of TNF alpha and caspase 3. It also inhibits the translocation of NFkB into the nuclei and conjugates free radicals. Some studies have shown a glycyrrhizic-driven inhibition of CD4+ T cell proliferation via JNK, ERK and PI3K/AKT.
The antiviral activity of glycyrrhizic acid includes the inhibition of viral replication and immune regulation. The antiviral activity of glycyrrhizic acid seems to be of a broad spectrum and be able to cover several different viral types such as vaccinia virus, herpes simplex virus, Newcastle disease virus and vesicular stomatitis virus.
The effect of glycyrrhizic acid on metabolism is thought to be related to its inhibitory activity towards 11-beta-hydroxysteroid dehydrogenase type 1 which in turn decreases the activity of hexose-6-phosphate dehydrogenase. On the other hand, some studies have shown a potential lipoprotein lipase induction in non-hepatic tissues and thus it is suggested to enhance dyslipidemic conditions.
Toxicity
Glycyrrhizin is thought to generate inhibition of 11-beta-hydroxysteroid dehydrogenase in the kidney which leads to elevated cortisol levels in the kidney. Intravenous administration of the ammoniated form was shown to produce convulsions and hemolysis.
Preclinical overdose studies have been shown to produce mineralocorticoid excess. The LD50 in preclinical studies was reported to be in the range of 308-12700 mg/kg.
Glycyrrhizin has been proven to not have mutagenic, genotoxic, teratogenic nor carcinogenic effects.
Food Interaction
No interactions found.Volume of Distribution
The apparent volume of distribution of glycyrrhizic acid either in the central compartment and in steady-state are in the range of 37-64 ml/kg and 59-98 ml/kg, respectively.
Elimination Route
Glycyrrhizin is mainly absorbed after presystemic hydrolysis and formation of glycyrrhetinic acid. Therefore, after oral administration of a dose of 100 mg of glycyrrhizic acid, this major metabolite appears in plasma in a concentration of 200 ng/ml while glycyrrhizic acid cannot be found. The finding of a minimal amount of glycyrrhizic acid in urine suggests the existence of a partial absorption in the gastrointestinal tract.
Half Life
Depending on the dose, the second elimination phase in humans has a half-life of 3.5 hours.
Clearance
The constant reabsorption of glycyrrhetic acid in the duodenum causes a delay in the terminal plasma clearance. The reported total body clearance of glycyrrhizic acid is reported to be in the range of 16-25 ml.kg/h.
Elimination Route
Glycyrrhizin presents a biphasic elimination from the central compartment with a dose-dependent second elimination phase. The majority of the administered dose is eliminated by the bile in which glycyrrhizic acid can be eliminated unchanged and undergoes enterohepatic cycling. On the other hand, the major metabolite, glycyrrhetinic acid, forms glucuronide and sulfate conjugates. These conjugates are efficiently transported into the bile and duodenum where commensal bacteria hydrolizes the conjugate for the formation of glycyrrhetinic acid and further reabsorption. This reabsorption behavior seems to be related to the activity of 3-alpha-hydroxysteroid dehydrogenase which transports very efficiently the metabolite from the plasma to the bile.
About 1.1-2.5% of the administered dose of glycyrrhizic acid can be found in urine which corresponds to the minimal cycling and reabsorption of this compound.
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