View source for Glycyrrhizin

{{short description|Main sweet-tasting constituent of liquorice}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| drug_name = Glycyrrhizic acid
| IUPAC_name = (3β,20β)-20-carboxy-11-oxo-30-norolean-12-en-3-yl 2-O-β-D-glucopyranuronosyl-α-D-glucopyranosiduronic acid
|   image = Glycyrrhizic Acid.svg
|   width = 280px
|   image2 = Glycyrrhizin zwitterion ball-and-stick xtal 2009.png
|   width2 = 250px

<!-- Clinical data-->
| tradename = Epigen, Glycyron
| Drugs.com = {{drugs.com|international|glycyrrhizin}}
| legal_status = <!-- Generally regarded as safe -- Not legal. -->
| routes_of_administration = Oral, intravenous

<!-- Pharmacokinetic data-->
| metabolism = Hepatic and by intestinal bacteria
| elimination_half-life = 6.2–10.2 hours<ref name="van_Rossum_1999">{{cite journal | vauthors = van Rossum TG, Vulto AG, Hop WC, Schalm SW | title = Pharmacokinetics of intravenous glycyrrhizin after single and multiple doses in patients with chronic hepatitis C infection | journal = Clinical Therapeutics | volume = 21 | issue = 12 | pages = 2080–2090 | date = December 1999 | pmid = 10645755 | doi = 10.1016/S0149-2918(00)87239-2 | hdl-access = free | hdl = 1765/73160 | url = https://pure.eur.nl/en/publications/25e2d17a-3123-40f6-9b23-2ca4ddbc0c97 }}</ref>
| excretion = Faeces, urine (0.31–0.67%)<ref>{{cite journal | vauthors = Ploeger B, Mensinga T, Sips A, Seinen W, Meulenbelt J, DeJongh J | title = The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling | journal = Drug Metabolism Reviews | volume = 33 | issue = 2 | pages = 125–147 | date = May 2001 | pmid = 11495500 | doi = 10.1081/DMR-100104400 | s2cid = 24778157 }}</ref>

<!-- Identifiers-->
| UNII = 6FO62043WK
| KEGG = D00157
| PubChem = 14982
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = LPLVUJXQOOQHMX-QWBHMCJMSA-N
| CAS_number = 1405-86-3
| CAS_supplemental =  (α-D-Glucopyranosiduronic acid), {{CAS|103000-77-7}} (β-D-Glucopyranosiduronic acid)
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 14263
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 441687
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 15939

| ATC_prefix=A05
| ATC_suffix=BA08
| ATCvet = 
| ATC_supplemental = QA05BA08 (vet)

<!-- Chemical data-->
| chemical_formula =
| C=42|H=62|O=16
| density = 
| solubility = 1–10
| 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
}}

'''Glycyrrhizin''' ('''glycyrrhizic acid'''  or '''glycyrrhizinic acid''') is the chief [[Sweetness|sweet-tasting]] constituent of ''Glycyrrhiza glabra'' ([[liquorice]]) root. Structurally, it is a [[saponin]] used as an [[emulsion|emulsifier]] and [[gel]]-forming agent in foodstuffs and [[cosmetics]]. Its [[aglycone]] is [[enoxolone]].

==Pharmacokinetics==
After oral ingestion, glycyrrhizin is [[hydrolysis|hydrolysed]] to 18β-glycyrrhetinic acid ([[enoxolone]]) by intestinal bacteria. After absorption from the gut, 18β-glycyrrhetinic acid is metabolised to 3β-monoglucuronyl-18β-glycyrrhetinic acid in the liver. This metabolite circulates in the bloodstream. Consequently, its oral bioavailability is poor.{{Quantify|date=November 2018}}<!-- Being a prodrug, it's probably more important to note the availablity for hydrolyzed enoxolone instead. --> Most of it is eliminated by [[bile]] and only a minor part (0.31–0.67%) by urine.<ref name="Glavac_2012">{{cite journal | vauthors = Glavač NK, Kreft S | title = Excretion profile of glycyrrhizin metabolite in human urine | journal = Food Chemistry | volume = 131 | pages = 305–308 | year = 2012 | doi = 10.1016/j.foodchem.2011.08.081 }}</ref> After oral ingestion of 600&nbsp;mg of glycyrrhizin the metabolite appeared in urine after 1.5 to 14 hours. Maximal concentrations (0.49 to 2.69&nbsp;mg/L) were achieved after 1.5 to 39 hours and metabolite can be detected in the urine after 2 to 4 days.<ref name="Glavac_2012" />

== Pharmacological action ==
The polypharmacological effect of glycyrrhizinic acid, which has at least 12 types of activity<ref name=":0">{{cite journal | vauthors = Ershov PV, Yablokov EO, Kaluzhskiy LA, Mezentsev YV, Gnedenko OV, Konstantinov MA, Toropygin IY, Ivanov AS | title = Glycyrrhizic acid: novel potential protein targets | journal = Biomeditsinskaia Khimiia | volume = 71 | issue = 4 | pages = 270–282 | date = September 2025 | pmid = 40904179 | doi = 10.18097/PBMCR1595 | language = ru }}</ref> (antitumor,<ref>{{cite journal | vauthors = Su X, Wu L, Hu M, Dong W, Xu M, Zhang P | title = Glycyrrhizic acid: A promising carrier material for anticancer therapy | journal = Biomedicine & Pharmacotherapy | volume = 95 | pages = 670–678 | date = November 2017 | pmid = 28886526 | doi = 10.1016/j.biopha.2017.08.123 }}</ref> hepatoprotective,<ref>{{cite journal | vauthors = Cao R, Gong H, Xia S, Hu Z, Fan X, Zhai B, Guo L, Xia C, Jiang Z, Yan M | title = Glycyrrhizic acid promotes liver regeneration through activating β-catenin in acetaminophen-induced liver injury | journal = Journal of Ethnopharmacology | volume = 349 | date = June 2025 | pmid = 40306499 | doi = 10.1016/j.jep.2025.119895 | article-number = 119895 }}</ref> immunomodulatory, antidiabetic, nephroprotective, cardioprotective, neuroprotective, atheroprotective, anti-inflammatory, antithrombotic, etc.), is closely related to its interaction with various cellular targets. Approximately 88 cellular proteins<ref name=":0" /> have been experimentally identified as potential targets of glycyrrhizic acid, including cytochromes P450, UDP-glucouronosyltransferases, oxidoreductases, and proteins involved in amino acid metabolism and steroid hormone biosynthesis.

==Flavouring properties==
Glycyrrhizin is obtained as an [[extract]] from licorice root after [[Liquid–liquid extraction|maceration]] and boiling in water.<ref name="fda">{{cite web | title = Sec. 184.1408 Licorice and licorice derivatives | date = 1 April 2017 | url = https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1408 | archive-url = https://web.archive.org/web/20030510182921/http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?FR=184.1408 | archive-date = May 10, 2003 | publisher = US Food and Drug Administration, Code of Federal Regulations Title 21, 21CFR184.1408 | access-date = 15 December 2017 }}</ref> Licorice extract (glycyrrhizin) is sold in the United States as a liquid, paste, or [[spray drying|spray-dried]] powder.<ref name="fda" /> When in specified amounts, it is approved for use as a flavor and [[odor|aroma]] in manufactured foods, beverages, candies, [[dietary supplement]]s, and [[seasoning]]s.<ref name="fda" /> It is 30 to 50 times as sweet as [[sucrose]] (table sugar).<ref name = pubchem>{{cite web | title = Glycyrrhizic Acid | work = PubChem | publisher = National Institutes of Health | access-date = 24 February 2014 | url = https://pubchem.ncbi.nlm.nih.gov/compound/14982 }}</ref>

==Adverse effects==
The most widely reported side effect of glycyrrhizin use via consumption of [[Liquorice (confectionery)|black liquorice]] is reduction of blood [[Potassium in biology|potassium]] levels, which can affect body [[fluid balance]] and function of [[nerve]]s.<ref name="fda-cons">{{cite web | title = Black Licorice: Trick or Treat? | date = 30 October 2017 | url = https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm277152.htm | archive-url = https://web.archive.org/web/20111027112735/http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm277152.htm | archive-date = October 27, 2011 | publisher = US Food and Drug Administration | access-date = 15 December 2017 }}</ref><ref name="Penninkilampi_2017">{{cite journal | vauthors = Penninkilampi R, Eslick EM, Eslick GD | title = The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis | journal = Journal of Human Hypertension | volume = 31 | issue = 11 | pages = 699–707 | date = November 2017 | pmid = 28660884 | doi = 10.1038/jhh.2017.45 | s2cid = 205168217 }}</ref> Chronic consumption of black licorice, even in moderate amounts, is associated with an increase in [[blood pressure]],<ref name="Penninkilampi_2017" /> may cause [[Heart arrhythmia|irregular heart rhythm]], and may have [[Drug interaction|adverse interactions]] with [[prescription drug]]s.<ref name="fda-cons" /> In extreme cases, death can occur as a result of excess consumption.<ref>{{cite news | vauthors = Marchione M | title = Too much candy: Man dies from eating bags of black licorice | url = https://apnews.com/04cf918055b735ea69483dd00e281253 | access-date = 24 September 2020 | work = AP News }}</ref><ref>{{cite journal | vauthors = Edelman ER, Butala NM, Avery LL, Lundquist AL, Dighe AS | title = Case 30-2020: A 54-Year-Old Man with Sudden Cardiac Arrest | journal = The New England Journal of Medicine | volume = 383 | issue = 13 | pages = 1263–1275 | date = September 2020 | pmid = 32966726 | pmc = 8568064 | doi = 10.1056/NEJMcpc2002420 }}</ref>

== See also ==
* [[11α-Hydroxyprogesterone]]
* [[Glycyrrhetinic acid]]
* [[List of unusual deaths in the 21st century]]

== References ==
{{Reflist}}

== External links ==
{{Commons category-inline}}

{{Glycosides}}
{{Bile and liver therapy}}
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[[Category:11β-Hydroxysteroid dehydrogenase inhibitors]]
[[Category:Triterpene glycosides]]
[[Category:Sugar substitutes]]
[[Category:Saponins]]