関: glycyrrhetinic acid

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/03/22 10:50:00」(JST)

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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 flavoring 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.^[1] It has some additional pharmacological properties including antiviral, antifungal, antiprotozoal, and antibacterial activities.^[2]^[3]^[4]^[5]

Mechanism of action

Glycyrrhetinic acid inhibits the enzymes (15-hydroxyprostaglandin dehydrogenase and delta-13-prostaglandin) that metabolize 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-β-D-(monoglucuronyl)-18-β-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-β-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.

Derivatives

Glycyrrhetinic acid derivatives, where R is a variable functional group

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.^[6] 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.

A synthetic analog, carbenoxolone, was developed in Britain.^{[citation needed]} Both glycyrrhetinic acid and carbenoxolone have a modulatory effect on neural signaling through gap junction channels.

Acetoxolone, the acetyl derivative of glycyrrhetinic acid, is a drug used in the treatment of peptic ulcer and gastroesophageal reflux disease.

Notes

^ Chandler, RF (1985). "Liquorice, more than just a flavour". Canadian Pharmaceutical Journal (118): 420–4.
^ Badam, L., Amagaya, S. and Pollard, B. (1997). "In vitro activity of licorice and glycyrrhetinic acid on Japanese encephalitis virus.". J. Community Dis. 29: 91–99.
^ Fuji, H.Y., Tian, J. and Luka, C. (1986). "Effect of glycyrrhetinic acid on influenza virus and pathogenic bacteria.". Bull. Chin. Mater. Med. 11: 238–241.
^ Guo, N., Takechi, M. and Uno, C. (1991). "Protective effect of glycyrrhizine in mice with systemic Candida albicans infection and its mechanism". J. Pharm. Pharmacol. 12 (5): 380–383. PMID 1839259.
^ Salari, M. H., Sohrabi, N., Kadkhoda, Z., and Khalili, M. B. (2003). "Antibacterial effects of Enoxolone on periodontopathogenic and capnophilic bacteria isolated from specimens of periodontitis patients". Iran. Biomed. J. 7: 39–42.
^ Ijichi, So; Seizo Tamagaki (2005). "Molecular Design of Sweet Tasting Compounds Based on 3β-Amino-3β-deoxy-18β-glycyrrhetinic Acid: Amido Functionality Eliciting Tremendous Sweetness". Chemistry Letters 34 (3): 356. doi:10.1246/cl.2005.356. http://www.jstage.jst.go.jp/article/cl/34/3/34_356/. Retrieved 2010-09-28.

References

Saponin Glycosides, by Georges-Louis Friedli, URL accessed Sept 2010.

English Journal

The influence of compatibility of processed radix Aconiti Kusnezoffii on the pharmacokinetic of four components in Glycyrrhiza uralensis Fisch.

Zhou B1, Zhang J2, Wu S1, Zhuo Q1, Gao W3, Hao J4, Man S1.
Journal of ethnopharmacology.J Ethnopharmacol.2015 Jul 1;169:1-7. doi: 10.1016/j.jep.2015.03.059. Epub 2015 Apr 16.
ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhiza uralensis Fisch. and processed radix Aconiti kusnezoffii are the main components in many Chinese traditional patent medicines with the ratio of 1:1, which are used for treatment of rheumatoid arthritis, heart failure and so on. Glycyrrhizic acid, glycyrrhe
PMID 25889555

18-β Glycyrrhetinic acid alleviates 2-acetylaminofluorene-induced hepatotoxicity in Wistar rats: Role in hyperproliferation, inflammation and oxidative stress.

Hasan SK1, Khan R1, Ali N1, Khan AQ1, Rehman MU1, Tahir M1, Lateef A1, Nafees S1, Mehdi SJ1, Rashid S1, Shahid A1, Sultana S2.
Human & experimental toxicology.Hum Exp Toxicol.2015 Jun;34(6):628-41. doi: 10.1177/0960327114554045. Epub 2014 Oct 28.
2-Acetylaminofluorene (2-AAF) is a known hepatic carcinogen which leads to tumour formation in rodents. 18-β Glycyrrhetinic acid (18β-GA) derived from liquorice plant has various pharmacological properties such as anti-ulcer, anti-inflammatory, antiviral, hepatoprotective and antioxidant. This stu
PMID 25352648

The importance of connexin hemichannels during chondroprogenitor cell differentiation in hydrogel versus microtissue culture models.

Schrobback K1, Klein TJ1, Woodfield TB1.
Tissue engineering. Part A.Tissue Eng Part A.2015 Jun;21(11-12):1785-94. doi: 10.1089/ten.TEA.2014.0691. Epub 2015 Mar 24.
Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell-cell communication an
PMID 25693425

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★リンクテーブル★

リンク元	「グリチルレチン酸」「エノキソロン」
拡張検索	「carbenoxolone sodium」

「グリチルレチン酸」

Glycyrrhetinic acid
	IUPAC name (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-icosahydropicene-2-carboxylic acid
	Other names Enoxolone; Glycyrrhetin; Uralenic acid; Glycyrrhetinate; Arthrodont; 3β-Hydroxy-11-oxoolean-12-en-30-olic acid
Identifiers
CAS number	471-53-4
PubChem	10114
ChemSpider	9710
ChEBI	CHEBI:30853
ChEMBL	CHEMBL230006
ATC code	D03AX10
Jmol-3D images	Image 1
	SMILES O=C(O)[C@]5(C)C[C@H]4/C3=C/C(=O)[C@H]1[C@](CC[C@@H]2[C@]1(C)CC[C@H](O)C2(C)C)(C)[C@]3(C)CC[C@@]4(C)CC5 ;
	InChI InChI=1S/C30H46O4/c1-25(2)21-8-11-30(7)23(28(21,5)10-9-22(25)32)20(31)16-18-19-17-27(4,24(33)34)13-12-26(19,3)14-15-29(18,30)6/h16,19,21-23,32H,8-15,17H2,1-7H3,(H,33,34)/t19-,21-,22-,23+,26+,27-,28-,29+,30+/m0/s1 ; Key: MPDGHEJMBKOTSU-YKLVYJNSSA-N InChI=1/C30H46O4/c1-25(2)21-8-11-30(7)23(28(21,5)10-9-22(25)32)20(31)16-18-19-17-27(4,24(33)34)13-12-26(19,3)14-15-29(18,30)6/h16,19,21-23,32H,8-15,17H2,1-7H3,(H,33,34)/t19-,21-,22-,23+,26+,27-,28-,29+,30+/m0/s1; Key: MPDGHEJMBKOTSU-YKLVYJNSBE ;
Properties
Molecular formula	C30H46O4
Molar mass	470.68 g mol−1
	(verify) (what is: /?); Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
	Infobox references