Medical Attributes of Glycyrrhiza glabra – Licorice

by Isaiah Pinkerton
Wilkes University, Wilkes-Barre, PA

July 2017

Licorice (Glycyrrhiza glabra) is an herbaceous perennial member of the legume family (Fabaceae) that is native to Europe and southern Asia - including India and China (Shibata 2000). Today, licorice is commonly used in Traditional Chinese Medicine (TCM) and western mainstream medicine (Kao, et al. 2014). The benefits currently being researched pertain to its anti-viral, antibacterial, and anti-cancer properties, as well as relieving menopausal associated inflictions. In the past few decades, the need for G. glabra has increased dramatically and the natural population of the species has been on the decline due to overuse in Balochistan region of southwestern Asia, where it is commercially cultivated (Dastagir & Rizvi 2016). 

G. glabra has been used since ancient times in Greece, Rome, and China. Many prominent botanists at the time including Theophrastus, Dioscorides, Plinius the Elder, and Galen recognized the medicinal and agricultural benefits of the root in particular in extractions, infusions and potions (Fiore, et al. 2005). Indeed, recorded in Plini Secundi Naturalis Historiae, Plinius the Elder recommended the root of the licorice plant to be used as a remedy for asthma, malaises, ulcers, kidney stones, skin lesions, and combat sterility, as well as an antispasmodic, and diuretic (Fiore, et al. 2005).

In modern times, the main component of the licorice root, glycyrrhizin, is used as a flavoring in tobacco, a confectionary sweetener in many food products, and a chief emulsifier in cosmetics (Fenwick 1990).

Licorice has various medicinal attributes that are associated with numerous bioactive components including its pure root extract, glabridin, glabrene, ethanol based extracts, carbenoxolone, glycyrrhizic acid, and ammonium glycyrrhizate. Animal studies demonstrated that glycyrrhizin, a saponin, reduced mortality and viral activity in herpes simplex virus encephalitis and influenza A virus pneumonia (Flore, et al. 2008). In vitro studies revealed antiviral activity against HIV-1, SARS related coronavirus, respiratory syncytial virus, arboviruses, vaccinia virus and vesicular stomatitis virus (Flore, et al. 2008, Pu, et al. 2013).

Another chemical component called glabridin, a major isoflavene, has been associated with a wide range of biological properties such as antioxidant, anti-inflammatory, anti-atherogenic, regulation of energy metabolism, estrogenic, neuroprotective, anti-osteoporotic, and skin-whitening (Simmler, et al. 2013). Glabridin is reported to posses the capacity to down-regulate intracellular reactive oxygen species, bind to antioxidant effectors, and act on estrogen receptors, potentially as a plant-based Selective Estrogen Receptor Modulator (Simmler, et al. 2013). In two separate studies, licorice (G. glabra) chemical derivative glabrene, another isoflavene, along with glabridin were evaluated for their efficacy in treating vascular tissue both in vitro and in vivo for post-menopausal women who have reported to have a high risk of heart disease. Both components exhibited activity similar to that of estrogen in order to modulate vascular injury and prevent cardiovascular disease by promoting atherogenesis (Somjen, et al. 2004; Somjen, et al. 2004, Simons, et al. 2011).

A broad spectrum of in vitro and in vivo studies have recently demonstrated that the mixed extracts and purified compounds from licorice exhibit anti-cancer properties by inhibition of proliferation, induction of cell cycle arrest, apoptosis, autophagy, differentiation, suppression of metastasis, angiogenesis, and sensitization of chemotherapy or radiotherapy (Tang, et al. 2015). A combined treatment of licorice compounds and clinical chemotherapy drugs remarkably enhances anti-cancer effects and reduces the side effects of chemotherapeutics (Tang, et al. 2015). The fatalities attributed to colorectal cancer have led to numerous studies, including in vitro evaluation of an ethanol extract of G. glabra affecting the gene expression of chaperone protein, HSP90. Observations of cell proliferation and apoptosis had confirmed the anti-cancer property, and will motivate extensive in vivo biological evaluation and subsequently lead to clinical evaluations (Nourazarian, et al. 2015).

Investigation into possible learning and memory benefits of licorice on mouse models have been tested. Extracts were shown to improve memory and enhance learning potential.  Furthermore, licorice extracts reduced the amnesia effect of diazepam and scopolamine (Dhingra, et al. 2004; Dhingra, et al. 2004, Chakravarthi, et al. 2013). Screening tests performed against certain strains of Mycobacterium tuberculosis establish that glabridin is an effective anti-bacterial agent (Gupta, et al. 2008).  Carbenoxolone, a steroidal derivative of glycyrrhetenic acid, is an effective treatment against peptic ulcers, both gastric and duodenal (Pinder, et al. 1976). Additionally, carbenoxolone has the capacity to prevent and reduce the progression of fatty acid liver disease in patients with insulin resistance (Rhee, et al. 2012).

The dangers of licorice include moderate chronic or high acute exposure to glycyrrhizic acid, ammonium glycyrrhizate, and their metabolites, that causes several transient systemic alterations.  They include increased potassium excretion, sodium and water retention, body weight gain, alkalosis, suppression of the renin-angiotensis-aldosterone system, hypertension, and muscular paralysis (Cosmetic Ingredient Review 2007). One account detailed a child with prolonged ingestion of an excess level of licorice leading to hemorrhagic gastritis (Wong, et al. 2012).

Glycyrrhiza glabra has been used for thousands of years for its medicinal and cultural attributes. Likewise, its active constituents including glycyrrhizin, glabridin, glabrene, carbenoxolone, glycyrrhizic acid, ammonium glycyrrhizate, and their metabolites all have proven medical benefits. The most prominent benefits include reduction of menopausal associated cardiovascular disease, relieving hepatic related inflammation, antibiotic/anti-viral, and anti-cancer properties. Overdosing on any of its chemical components is rare and seldom leads to fatality.



LITERATURE CITED:

Chakravarthi, K.K. & R. Avadhani. 2013. Beneficial effect of aqueous root extract of Glycyrrhiza glabra on learning and memory using different behavioral models: an experimental study. J Nat Sci Biol Med. 2013. 4(2): 420-25.

Cosmetic Ingredient Review Expert Panel. 2007. Final report on the safety assessment of Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Disodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate, and Potassium Glycyrrhizinate. Int J Taxicol. 2: 79-112.

Dastagir, G. & M.A. Rizvi. 2016. Review – Glycyrrhiza glabra L. (licorice). Pak J Pharm Sci. 29(5): 1727-1733).

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Fiore, C. & M. Eisenhut & R. Krausse & E. Ragazzi & D. Pellati & D. Armanini & J. Bielenberg. 2008. Antiviral effects of Glycyrrhiza glabra. Phytother Res. 22(2): 141-8.

Gupta, V.K. et al. 2008. Antimicrobial potential of Glycyrrhiza glabra roots. Journal of Ethnopharmacology. 116(2): 377-80.

Kao, T.C. & C.H. Wu & G.C. Yen. 2014. Bioactivity and potential health benefits of licorice. J Agric Food Chem. 62(3): 542-53.

Nourazarian, S.M. & A. Nourazarian & M. Majidinia & E. Roshaniasi. 2015. Effect of root extracts of medicinal herb Glycyrrhiza glabra on HSP90 gene expression and apoptosis in the HT-29 colon cancer cell line. Asian Pac J Cancer Prev. 16(18): 8563-6.

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Somjen, D. & S. Katzburg & J. Vaya & A.M. Kaye & D. Hendel & G.H. Posner & S. Tamir. 2004. Estrogenic activity of glabridin and glabrene from licorice roots on human osteoblasts and prepubertal rat skeletal tissues. J Steroid Biochem Mol Biol. 91(4-5): 241-6.

Tang, Z.H. & T. Li & Y.G. Tong & X.J. Chen & X.P. Chen & Y.T. Wang & J.J. Lu. 2015. A systematic review of the anticancer properties of compounds isolated from licorice (Gancao). Planta Med. 81(18): 1670-87.

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This paper was developed as part of the BIO 368 - Medical Botany course offered at Wilkes University during the summer of 2017. Course instructor was Kenneth M. Klemow, Ph.D. (kklemow@wilkes.edu). The information contained herein is based on published sources, and is made available for academic purposes only. No warrantees, expressed or implied, are made about the medical usefulness or dangers associated with the plant species in question.

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This page posted and maintained by Kenneth M. Klemow, Ph.D., Biology Department, Wilkes University, Wilkes-Barre, PA 18766. (570) 408-4758, kklemow@wilkes.edu.