Glycyrrhizic acid (GA), belonging to a class of triterpenes, is a conjugate of two molecules, namely glucuronic acid and glycyrrhetinic acid. It is naturally extracted from the roots of licorice plants. With its more common uses in the confectionery and cosmetics industry, GA extends its applications as a herbal medicine for a wide range of ailments. At low appropriate doses, anti-inflammatory, anti-diabetic, antioxidant, anti-tumor, antimicrobial and anti-viral properties have been reported by researchers worldwide. This review summarizes the effects of GA on metabolic syndrome, tumorigenesis, microbes and viruses, oxidative stress, and inflammation, as well as the reported side effects of the drug.
HertzW., MooreR.E., FukaiT., NomuraT., KirbyG.W. (1998) Progress in the chemistry of organic natural products.Vienna, Austria: Springer, 5–7.
3.
BaltinaL.A. (2003) Chemical modification of glycyrrhizic acid as a route to new bioactive compounds for medicine. Current Medicinal Chemistry, 10, 155–177.
4.
SaleemMMNMSA, MohammadA.A.W., Al-TameemiJ.A., SulaimanG.M. (2011) Biological study of the effect of licorice roots extract on serum lipid profile, liver enzymes and kidney function tests in albino mice. African Journal of Biotechnology, 10, 12702–12706.
5.
ChiaY.Y., TonS.H., KhalidB.A.K. (2009) Effects of glycyrrhizic acid on peroxime proliferator-activated receptor gamma (PPAR-γ), lipoprotein lipase (LPL), serum lipid and HOMA-IR is rats. PPAR Research, 6, 125–141.
6.
EuC.H., LimW.A.Y., AbdulK.K. (2010) Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet-induced obese rats. Lipids in Health and Disease, 29, 81–90.
7.
ChiaY Y., TonS.H., KhalidB.A.K. (2012) Amelioration of glucose homeostasis by glycyrhizzic acid through gluconeogenesis rate limiting enzymes. European Journal of Pharmacology, 677, 197–202.
8.
ChandramouliC., YongS.T., LamY.L., TonS.H., KhalidB.A.K. (2011) Glycyrrhizic acid improves lipid and glucose metabolism in high-sucrose-fed rats. Journal of Endocrinology and Metabolism, 1, 125–141.
9.
RadwanM.A., Aboul-EneinH.Y. (2002) The effect of oral absorption enhancers on the in vivo performance of insulin-loaded poly(ethylcyanocrylate) nanospheres in diabetic rats. Journal of Microencapsulation, 19, 225–235.
10.
SugiiS., OlsonP., SearsD.D., SaberiM., AtkinsA.R., BarishG.D., HongS.H., CastroG.L., YinY.Q., NelsonM.C., HsiaoG., GreavesD.R., DownesM., YuR.T., OlefskyJ.M., EvansR.M. (2009) PPAR gamma activation in adipocytes is sufficient for systemic insulin sensitization. The National Academy of Sciences, 106, 22504–22509.
11.
MauryaS.K., SrivastavaA.K. (2011) Glycyrrhizic acid attenuates the expression of HMG-CoA reductase mRNA in high fructose diet induced dyslipidemic hamsters. Prague Medical Report, 112, 29–37.
12.
HomburgR. (2009) Androgen circle of polycystic ovary syndrome. Human Reproduction, 24, 1548–1555.
13.
GambineriA., PelusiC., VicennatiV., PagottoU., PasqualiR. (2002) Obesity and the polycystic ovary syndrome. International Journal of Obesity, 26, 883–896.
14.
Gomez-SanchezE.P., Gomez-SanchezC.E. (1992) Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone. American Journal of Physiology, 263, 1125–1130.
15.
CherngJ.M., TsaiK.B., YuY.W., LinJ.C. (2011) Molecular mechanisms underlying chemoprotective activities of glycyrrhizic acid against UVB-radiation-induced carcinogenesis in SKH-1 hairless mouse epidermis. Radiation Research, 176, 177–186.
16.
ChungJ.G., ChangH.L., WangH.H., YehC.C., HungC.F., LiY.C. (2000) Inhibition of N-acetyltransferase activity and DNA-2-aminofluorene adducts by glycyrrhizic acid in human colon tumour cells. Food and Chemical Toxicology, 38, 163–172.
17.
ZhangM.Z., XuJ., YaoB., YinH., CaiQ., ShrubsoleM.J., ChenX., KonV., ZhengW., PozziA., HarrisR.C. (2009) Inhibition of 11β-hydroxysteroid dehydrogenase type II selectively blocks the tumor COX-2 pathway and suppresses colon carcinogenesis in mice and humans. The Journal of Clinical Investigation, 119, 876–885.
18.
CurreliF., Friedman-KienA.E., FloreO. (2005) Glycyrrhizic acid alters Kaposi sarcoma-associated herpes virus latency, triggering p53-mediated apoptosis in transformed B lymphocytes. Journal of Clinical Investigation, 115, 642–652.
19.
KaurP., SharmaN., SinghB., KumarS., KaurS. (2012) Modulation of genotoxicity of oxidative mutagens by glycyrrhizic acid from Glycyrrhiza glabra L. Pharmacognosy Research, 4, 189–195.
20.
RaphaelT.J., KuttanG. (2008) Effect of naturally occurring triterpenoids ursolic acid and glycyrrhizic acid on the cell-mediated immune responses of metastatic tumour-bearing animals. Immunopharmacology and Imumunotoxicology, 30, 243–255.
21.
HaleagraharaN., VarkkeyJ., ChakravarthiS. (2011) Cardioprotective effects of glycyrrhizic acid against isoprotenerol-induced myocardial ischemia in rats. International Journal of Molecular Sciences, 12, 7100–7113.
22.
ChanH.T., ChanC., HoJ.W. (2003) Inhibition of glycyrrhizic acid on aflatoxin B1-induced cytotoxicity in hepatoma cells. Toxicology., 188, 211–217.
23.
PolyakovN.E., LeshinaT.V., SalakhutdinovN.F., KonovalovaT.A., KispertL.D. (2006) Antioxidant and redox properties of supramolecular complexes of carotenoids with β-glycyrrhizic acid. Free Radical Biology and Medicine, 40, 1804–1809.
BabaM., ShigetaS. (1987) Antiviral activity of glycyrrhizin against varicella-zoster virus in vitro.Antiviral Research, 7, 99–107.
27.
HoeverG., BaltinaL., MichaelisM., KondratenkoR., BaltinaL., TolstikovG.A., DoerrH.W., CinatlJ.J. (2005) Antiviral activity of glycyrrhizic acid derivatives against SARS-coronavirus. Journal of Medicinal Chemistry, 48, 1256–1259.
28.
LinJ.C., CherngJ.M., HungM.S., BaltinaL.A., BaltinaL., KondratenkoR. (2008) Inhibitory effects of some derivatives of glycyrrhizic acid against Epstein-Barr virus infection: Structure-activity relationships. Antiviral Research, 79, 6–11.
29.
ChungJ.G. (1998) Inhibitory actions of glycyrrhizic acid on arylamine N-acetyltransferase activity in strains of Helicobacter pylori from peptic ulcer patients. Drug and Chemical Toxicology, 21, 355–370.
30.
BhattacharjeeS., BhattacharjeeA., MajumderS., MajumdarS.B., MajumbarS. (2012) Glycyrrhiciz acid suppresses Cox-2-mediated anti-inflammatory responses during Leishmania donovani infection. Journal of Antimicrobial and Chemotherapy, 67, 1905–1914.
31.
KaoT.Z., ShyuM.H., YenG.C. (2010) Glycyrrhizic acid and 18β-glycyrrhetinic acid inhibit inflammation via P13L/Akt/GSK3β signaling and glucocorticoid receptor activation. Journal of Agricultural and Food Chemistry, 58, 8623–8629.
32.
SaeediM., SemnaniK.M., GhoreishiM.R. (2003) The treatment of atopic dermatitis with licorice gel. Journal of Dermatological Treatment, 14, 153–157.
33.
StormerF.C., ReistadR., AlexanderJ. (1993) Glycyrrhizic acid in liquorice – evaluation of health hazard. Food and Chemical Toxicology., 31, 303–312.
34.
CelikM.M., KarakusA., ZerenC., DemirM., BayarogullariH., DuruM., AlM. (2012) Licorice induced hypokalemia, edema, and thrombocytopenia. Human and Experimental Toxicology, 31, 1295–1298.
35.
(a) JohnsC. (2009) Glycyrrhizic acid toxicity caused by consumption of licorice candy cigars. Canadian Journal of Emergency Medicine, 94–96. (b) Zenone T, Blanc Q. (2009) Rhabdomyolosis with major hypokalemia secondary to chronic glycyrrhizic acid ingestion. La Revue de Medecine Interne, 30, 78-80.
36.
van BeersE.J., StamJ., van Den BerghM. (2011) Licorice consumption as a cause of posterior reversible encephalopathy syndrome: a case report. Critical Care, 15, R64–69.
37.
ZhangH., WangX.F., WuJ. (2011) Licorice consumption-associated thunderclap headache: posterior reversible encephalopathy syndrome or subarachnoid hemorrhage?Critical Care, 15, 416–417.
38.
van GelderenC.E.M., BijlsmaJ.A., van DokkumW., SavelkoulT.J.F. (2000) Glycyrrhizic acid: the assessment of a no effect level. Human and Experimental Toxicology, 19, 434–439.
