Glycyrrhetinic acid

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ImageFile=Glycyrrhetinic acid.pngImageSize=200px
IUPACName= 3β-hydroxy-11-oxoolean-12-en-30-oic acid
OtherNames=Enoxolone
Glycyrrhetin
Uralenic acid
Glycyrrhetinate
Arthrodont
Section1= Chembox Identifiers
CASNo=471-53-4
PubChem=10114
SMILES=CC1( [C@@H] 2CC [C@@] 3( [C@@H] ( [C@] 2(CC [C@@H] 1O)C)C(=O)C=C4 [C@] 3(CC [C@@] 5( [C@H] 4C [C@@] (CC5)(C)C(=O)O)C)C)C)C
Section2= Chembox Properties
Formula=C₃₀H₄₆O₄
MolarMass=470.68 g/mol
Appearance=
Density=
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Section3= Chembox Hazards
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Glycyrrhetinic acid is a pentacyclic triterpenoid derivative of the beta-amyrin type obtained from the hydrolysis of glycyrrhizic acid, which was obtained from the herb liquorice. It is used in flavouring and it masks the bitter taste of drugs like aloe and quinine. It is effective in the treatment of peptic ulcer and also has expectorant (antitussive) properties (Chandler,1985).

A synthetic analog, carbenoxolone, was developed in Britain. Both glycyrrhetinic acid and carbenoxolone have a modulatory effect on neural signaling through gap junction channels.

Glycyrrhetinic acid inhibits the enzymes (15-hydroxyprostaglandin dehydrogenase and delta-13-prostaglandin) that metabolise the prostaglandins PGE-2 and PGF-2α to their respective 15 keto-13,14-dihydro metabolites which are inactive. This causes an increased level of prostaglandins in the digestive system. Prostaglandins inhibit gastric secretion but stimulate pancreatic secretion and mucous secretion in the intestines and markedly increase intestinal motility. They also cause cell proliferation in the stomach. The effect on gastric acid secretion, promotion of mucous secretion and cell proliferation shows why licorice has potential in treating peptic ulcer.

PGF-2α stimulates activity of the uterus during pregnancy and can cause abortion, therefore, licorice should not be taken during pregnancy.

The structure of glycyrrhetinic acid is similar to that of cortisone. Both molecules are flat and similar at position 3 and 11. This might be the basis for licorice's anti-inflammatory action.

3-Beta-D-(monoglucuronyl)18-beta-glycyrrhetinic acid, a metabolite of glycyrrhetinic acid inhibits the conversion of "active" cortisol to "inactive" cortisone in the kidneys. This occurs via inhibition of the enzyme by inhibiting the enzyme 11-beta-hydroxysteroid dehydrogenase. As a result, cortisol levels are high within the collecting duct of the kidney. Cortisol has intrinsic mineralocorticoid properties (that is, it acts like aldosterone and increases sodium reabsorption) that work on ENaC channels in the collecting duct. Hypertension develops due to this mechanism of sodium retention. People often have high blood pressure with a low renin and low aldosterone blood level. The increased amounts of cortisol binds to the unprotected, unspecific mineralocorticoid receptors and induce sodium and fluid retention, hypokalaemia, high blood pressure and inhibition of the renin-angiotensin-aldosterone system. Therefore licorice should not be given to patients with a known history of hypertension.

In glycyrrhetinic acid the functional group (R) is a hydroxyl group. Research in 2005 demonstrated that with a proper functional group a very effective glycyrrhetinic artificial sweetener can be obtained. ["Molecular Design of Sweet Tasting Compounds Based on 3-Amino-3-deoxy-18-glycyrrhetinic Acid: Amido Functionality Eliciting Tremendous Sweetness" So Ijichi Seizo Tamagaki Chemistry Letters Vol. 34 (2005) , No. 3 p.356 [http://www.jstage.jst.go.jp/article/cl/34/3/34_356/_article Abstract] ] When R is an anionic NHCO(CH₂)CO₂K side chain, the sweetening effect is found to 1200 times that of sugar (human sensory panel data). A shorter or longer spacer reduces the sweetening effect. One explanation is that the taste bud cell receptor has 1.3 nanometers (13 angstroms) available for docking with the sweetener molecule. In addition the sweetener molecule requires three proton donor positions of which two reside at the extremities to be able to interact efficiently with the receptor cavity.

References

* [http://www.friedli.com/herbs/phytochem/glycosides.html#saponin Saponin Glycosides] , by Georges-Louis Friedli, URL accessed Dec 2007.