Glycyrrhizin

Glycyrrhizic acid

Clinical data
Trade names	Epigen, Glycyron
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral, intravenous
ATC code	A05BA08 (WHO)
Legal status
Legal status	Generally regarded as safe
Pharmacokinetic data
Metabolism	Hepatic and by intestinal bacteria
Biological half-life	6.2-10.2 hours[1]
Excretion	Faeces, urine (0.31-0.67%)[2]
Identifiers
IUPAC name (3β,20β)-20-carboxy-11-oxo-30-norolean-12-en-3-yl 2-O-β-D-glucopyranuronosyl-α-D-glucopyranosiduronic acid
CAS Number	1405-86-3 (α-D-Glucopyranosiduronic acid), 103000-77-7 (β-D-Glucopyranosiduronic acid)
PubChem (CID)	128229
ChemSpider	14263
UNII	6FO62043WK
ChEBI	CHEBI:15939
ChEMBL	CHEMBL441687
E number	E958 (glazing agents, ...)
ECHA InfoCard	100.014.350
Chemical and physical data
Formula	C42H62O16
Molar mass	822.93 g/mol
3D model (Jmol)	Interactive image
Solubility in water	1-10 mg/mL (20 °C)
SMILES O=C(O)[C@H]7O[C@@H](O[C@@H]6[C@@H](O)[C@H](O)[C@H](O[C@@H]6O[C@@H]2C(C)(C)[C@@H]3CC[C@@]1(C)[C@]5(C(=C/C(=O)[C@@H]1[C@@]3(C)CC2)\[C@@H]4C[C@](C(=O)O)(C)CC[C@]4(C)CC5)C)C(=O)O)[C@H](O)[C@@H](O)[C@@H]7O
InChI InChI=1S/C42H62O16/c1-37(2)21-8-11-42(7)31(20(43)16-18-19-17-39(4,36(53)54)13-12-38(19,3)14-15-41(18,42)6)40(21,5)10-9-22(37)55-35-30(26(47)25(46)29(57-35)33(51)52)58-34-27(48)23(44)24(45)28(56-34)32(49)50/h16,19,21-31,34-35,44-48H,8-15,17H2,1-7H3,(H,49,50)(H,51,52)(H,53,54)/t19-,21-,22-,23-,24-,25-,26-,27+,28-,29-,30+,31+,34-,35-,38+,39-,40-,41+,42+/m0/s1 Key:LPLVUJXQOOQHMX-QWBHMCJMSA-N

Glycyrrhizin (or glycyrrhizic acid or glycyrrhizinic acid) is the chief sweet-tasting constituent of Glycyrrhiza glabra (liquorice) root. Structurally it is a saponin and has been used as an emulsifier and gel-forming agent in foodstuff and cosmetics. Its aglycone is enoxolone and it has therefore been used as a prodrug for that compound, for example it is used in Japan to prevent liver carcinogenesis in patients with chronic hepatitis C.^[3]

Medical uses

Glycyrrhizin inhibits liver cell injury and is given intravenously for the treatment of chronic viral hepatitis and cirrhosis in Japan.^[4][5] It has also proven itself effective in the treatment of autoimmune hepatitis in one clinical trial.^[6]

Adverse effects

The most widely reported side effects of glycyrrhizin use are fluid retention. These effects are related to the inhibition of cortisol metabolism within the kidney, and the subsequent stimulation of the mineralocorticoid receptors.^[7] Other side effects include:^[8]

• Headache
• Paralysis
• Transient visual loss
• Torsades de pointes
• Tachycardia
• Cardiac arrest
• Hypokalaemia
• Reduced testosterone
• Premature birth
• Acute kidney failure
• Muscle weakness
• Myopathy
• Myoglobinuria
• Rhabdomyolysis
• Increased body weight

Mechanism of action

It inhibits the enzyme 11beta-hydroxysteroid dehydrogenase, which likely contributes to its anti-inflammatory and mineralocorticoid activity.^[8] It has a broad-spectrum of antiviral activity in vitro against:^[8][9]

• Herpes simplex virus,^[10] which has also been confirmed in vivo.^[11]
• Influenzavirus (including H5N1)^[12]
• Varicella zoster virus^[13]
• SARS coronavirus
• HIV
• Hepatitis A virus
• Hepatitis B virus
• Hepatitis C virus
• Hepatitis E virus
• Epstein–Barr virus
• Human cytomegalovirus
• Flavivirus
• Japanese encephalitis virus

Pharmacokinetics

After oral ingestion, glycyrrhizin is first hydrolysed to 18β-glycyrrhetinic acid by intestinal bacteria. After complete absorption from the gut, β-glycyrrhetinic acid is metabolised to 3β-monoglucuronyl-18β-glycyrrhetinic acid in the liver. This metabolite then circulates in the bloodstream. Consequently its oral bioavailability is poor. The main part is eliminated by bile and only a minor part (0.31–0.67%) by urine.^[14] After oral ingestion of 600 mg of glycyrrhizin the metabolite appeared in urine after 1.5 to 14 hours. Maximal concentrations (0.49 to 2.69 mg/l) were achieved after 1.5 to 39 hours and metabolite can be detected in the urine after 2 to 4 days.^[14]

Organoleptic properties

It is 30-50 times as sweet as sucrose (table sugar).^[8][15]

See also

• Glycyrrhetinic acid
• 11α-Hydroxyprogesterone

References

1. van Rossum, TG; Vulto, AG; Hop, WC; Schalm, SW (December 1999). "Pharmacokinetics of intravenous glycyrrhizin after single and multiple doses in patients with chronic hepatitis C infection.". Clinical Therapeutics. 21 (12): 2080–90. doi:10.1016/S0149-2918(00)87239-2. PMID 10645755.
2. Ploeger, B; Mensinga, T; Sips, A; Seinen, W; Meulenbelt, J; DeJongh, J (May 2001). "The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling.". Drug Metabolism Reviews. 33 (2): 125–47. doi:10.1081/DMR-100104400. PMID 11495500.
3. Arase, Yasuji; Ikeda, Kenji; Murashima, Naoya; Chayama, Kazuaki; Tsubota, Akihito; Koida, Isao; Suzuki, Yoshiyuki; Saitoh, Satoshi; Kobayashi, Masahiro; Kumada, Hiromitsu (15 April 1997). "The long term efficacy of glycyrrhizin in chronic hepatitis C patients". Cancer. 79 (8): 1494–1500. doi:10.1002/(SICI)1097-0142(19970415)79:8<1494::AID-CNCR8>3.0.CO;2-B.
4. Sato, H; Goto, W; Yamamura, J; Kurokawa, M; Kageyama, S; Takahara, T; Watanabe, A; Shiraki, K (May 1996). "Therapeutic basis of glycyrrhizin on chronic hepatitis B.". Antiviral Research. 30 (2-3): 171–7. doi:10.1016/0166-3542(96)00942-4. PMID 8783808.
5. van Rossum, TG; Vulto, AG; de Man, RA; Brouwer, JT; Schalm, SW (March 1998). "Review article: glycyrrhizin as a potential treatment for chronic hepatitis C." (PDF). Alimentary Pharmacology & Therapeutics. 12 (3): 199–205. doi:10.1046/j.1365-2036.1998.00309.x. PMID 9570253.
6. Yasui, S; Fujiwara, K; Tawada, A; Fukuda, Y; Nakano, M; Yokosuka, O (December 2011). "Efficacy of intravenous glycyrrhizin in the early stage of acute onset autoimmune hepatitis.". Digestive Diseases and Sciences. 56 (12): 3638–47. doi:10.1007/s10620-011-1789-5. PMID 21681505.
7. Ferrari, P.; Sansonnens, A.; Dick, B.; Frey, F. J. (2001). "In Vivo 11 -HSD-2 Activity: Variability, Salt-Sensitivity, and Effect of Licorice". Hypertension. 38 (6): 1330–6. doi:10.1161/hy1101.096112. PMID 11751713.
8. Asl, MN; Hosseinzadeh, H (June 2008). "Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds." (PDF). Phytotherapy Research. 22 (6): 709–24. doi:10.1002/ptr.2362. PMID 18446848.
9. Shamsa, F; Ohtsuki, K; Hasanzadeh, E; Rezazadeh, S (2010). "The Anti-inflammatory and Anti-viral Effects of an Ethnic Medicine: Glycyrrhizin" (PDF). Journal of Medicinal Plants. 9 (Suppl. 2): 1389.
10. Pompei, Raffaello; Flore, Ornella; Marccialis, Maria Antonietta; Pani, Alessandra; Loddo, Bernardo (1979). "Glycyrrhizic acid inhibits virus growth and inactivates virus particles". Nature. 281 (5733): 689–90. doi:10.1038/281689a0. PMID 233133.
11. Sekizawa, T; Yanagi, K; Itoyama, Y (February 2001). "Glycyrrhizin increases survival of mice with herpes simplex encephalitis.". Acta Virologica. 45 (1): 51–4. PMID 11394578.
12. Michaelis, Martin; Geiler, Janina; Naczk, Patrizia; Sithisarn, Patchima; Leutz, Anke; Doerr, Hans Wilhelm; Cinatl, Jindrich (2011). Pekosz, Andrew, ed. "Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza a Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression". PLoS ONE. 6 (5): e19705. doi:10.1371/journal.pone.0019705. PMC 3096629. PMID 21611183.
13. Baba, M; Shigeta, S (February 1987). "Antiviral activity of glycyrrhizin against varicella-zoster virus in vitro.". Antiviral Research. 7 (2): 99–107. doi:10.1016/0166-3542(87)90025-8. PMID 3034150.
14. Kočevar Glavač, Nina; Kreft, Samo (2012). "Excretion profile of glycyrrhizin metabolite in human urine". Food Chemistry. 131: 305–308. doi:10.1016/j.foodchem.2011.08.081.
15. "Glycyrrhizic Acid". PubChem. National Institutes of Health. Retrieved 24 February 2014.

External links

• CHEMICAL MODIFICATION OF GLYCYRRHIZIC ACID AS A ROUTE TO NEW BIOACTIVE COMPOUNDS FOR MEDICINE by L.A.Baltina; doi:10.2174/0929867033368538