Abstract

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Licorice root is an extremely versatile herb used both in traditional and modern medicinal applications. It is a member of the Leguminosae/Fabaceae family with two common varieties viz. Chinese licorice (Glycyrrhiza glabra) and American licorice (Glycyrrhiza uralensis), with the former being the most predominantly available. The dried roots of licorice contain many triterpenoids and hundreds of flavonoids working synergistically to support the medicinal qualities of this herb. Medicinal applications include use as an anti-inflammatory, anti-bacterial, anti-fungal, anti-diabetic, antiviral, anti-ulcer, antitussive, anti-oxidant, skin whitening, anti-diuretic agent. This article is a review of various available literature regarding traditional and modern applications of Glycyrrhiza spp.

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1. Introduction

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The state of the world health care system is in nothing short of a crisis. Pharmaceutical medicines are producing arguably extreme adverse effects on the human populace. Pharmaceutical companies have long skirted the damages caused by their medicines by marketing them as “potential side-effects”; however, side-effects are merely direct-effects which produce undesired results in the patient. These undesired effects driven by pharmaceutical medications has majorly influenced a revival of herbal remedies. Herbs which are recognized as generally safe to consume typically come with minimal to no undesired effects to human health. One of these herbs that has come back to the attention of the general populace is *Glycyrrhiza spp.*

*Glycyrrhiza spp.* is one of the most commonly referred to medicines in both Chinese and Ayurvedic medicine. There is an old Chinese saying which states, “nine out of ten formulas contain licorice root.”1 The name *Glycyrrhiza* is derived from the Greek *γλυκύς* (glukus), meaning "sweet", and *ῥίζα* (rhiza), meaning "root".2 It contains a compound known as Glycyrrhizin (GL) which is known to be 50-100x sweeter than sucrose.3 Common names for this herb are licorice root, sweet-root, and sweet-wood. The profile is sweet with a lingering licorice aftertaste. It is mildly cooling and moistening.

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2. Bioactive constituents

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Many different constituents have been isolated from *Glycyrrhiza glabra* with 40-50% of the dried plant material weight being water-soluble, biologically active compounds. Starches (30%), pectins, polysaccharides, simple sugars, gums, mucilage (Rhizome), amino acids, triterpene saponin, flavonoids, mineral salts, bitters, asparagines, tannins, glycosides, resins, sterols, volatile oils and various other substances are found in this complex. GL is the main active constituent which comprises 10-25% of the licorice root extract.4 GL is a triterpene glycoside saponin containing a 5 carbon ring structures bound to two glucose moieties. The aglycone of GL is known as Glycyrrhetic acid (GA).3 As a tribasic acid, GL appears in several salt forms. It occurs naturally in the licorice plant as potassium and calcium salts.4 The ammoniated salt of GL is manufactured for commercial use. Specifications for this salt have been established by the FDA.5 *Glycyrrhiza glabra* owes its yellow color to its various flavonoid content. Flavonoid rich fractions include liquiritigenin (LTG), liquiritin, licuraside, isoliquiritin, liquiritigenin, and licochalcone A (LCA), glabradin (GLD) among others.6 Five new flavonoids were recently isolated - glucoliquiritin apioside (a flavanone bisdesmoside), prenyllicoflavone A (a bisprenylflavone), shinflavanone (a prenylated pyranoflavanone), shinpterocarpin, and 1-methoxyphaseollin.7 Many volatile compounds have been isolated from the roots of Glycyrrhiza of which include Carvone, Methyl chavicol, α-Terpineol, 5-Methyl-Furfural, Thymol, Carvacrol, Eugenol, and various others.8

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3. Traditional uses

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Licorice root has been regularly paired with other herbs in order to harmonize the qualities of other herbs in traditional Chinese medicine (TCM) mixtures for centuries.10 Licorice root has been used in TCM to treat upper respiratory infections, bronchitis, stomach and spleen qi deficiency, poor appetite, loose stools, and more.9 Licorice root in Iran has found its way into different applications for its anti-inflammatory and anti-microbial properties.9 The Greeks used licorice root to treat asthma and coughs, diseases affecting the voice, and diseases of the lungs.9 Pliny suggested that licorice be used as a remedy for asthma, malaises of the throat, and ulcerations of the mouth in his Naturalis Historia of Plinius (~77 AD).11 Furthermore, licorice root was used as an herbal medicine that could treat artery diseases, heart palpitations, and angina in Germany during the Middle Ages.9 Licorice root has been found to be used in both cosmetics and as food additives due to its anti-microbial properties.9 Cosmetics produced in Japan have frequently contained licorice root extracts. Licorice root also produces an anti-inflammatory effect which makes it great for use in creams, lotions, and other topicals. Licorice root also contains saponins which gives it the ability to mix polar and nonpolar components used in cosmetics.9 American folk magic states that carrying a cross made by tying two sticks together with red yarn will protect one against injury and negativity.5 Most commonly, however, licorice root has been associated as a symbol of love and sex.12

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4. Pharmacological activity in literature

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4.1 Anti-inflammatory activity

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Reports show that GL and its aglycone, GA, show great anti-inflammatory properties. Their action on this response is similar to that of glucocorticoids and mineralocorticoids. GA was shown to inhibit all factors responsible for the body’s inflammation response during in vitro studies. It inhibits cyclooxygenase activity and prostaglandin formation.13

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4.2 Antiviral activity

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Research shows GL to be an effective antiviral against vaccinia, herpes simplex 1, Newcastle disease, vesicular stomatitis. Results of this study showed GL irreversibly inactivates the herpes simplex 1 virus.14 In vitro studies were able to show that GL effectively inhibits the replication of the Human-Immunodeficiency virus.15 GL has also been shown to be effective in suppressing replication of the SARS-coronavirus.16 GL inhibits influenza’s capability of binding to DNA, in turn reducing its ability to replicate.17 GA was shown to reduce rotovirus yields by 99% subsequent to viral inoculation. Levels of viral proteins VP2, VP6, and NSP2 were all significantly reduced.18 GA inhibited the human respiratory syncytial virus through several mechanisms, including preventing viral attachment.19

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4.3 Antimicrobial activity

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Recent studies over the years have shown that components of Glycyrrhiza spp. possess significant antimicrobial properties against both Gram-positive and Gram-negative bacteria, such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Bacillus subtilis.20-23 GA was shown to decrease the expression of SaeR and Hla, key virulence genes of Methicillin-resistant staphylococcus aureus, which produced bactericidal activity in GA and effectively destroyed MRSA.20 LCA and GLD were shown to significantly inhibited biofilm production and hyphal transition of C. albicans producing fungicidal activity.24 LTG has been shown to prevent the production of α-hemolysin, an important exotoxin in the pathogenesis of S. aureus, thereby protecting the body against staphylococcal infections.25 In brief, the antimicrobial activity of Glycyrrhiza spp. is in most part due to GA, LCA, GLD, and LTG.

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4.4 Anti-ulcer activity

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Recent studies have begun to show that most patients with ulcers are simultaneously infected with Helicobacter pylori.26 Due to its antibacterial activity against H. pylori, GL has been strongly implicated as a progressive treatment for ulcers.27

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4.5 Anti-malaria activity

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LCA has been reported to show significant activity against malaria. In vivo studies in mice with P. yoelii showed that LCA was able to eradicate the malaria parasite completely with no toxicity at 1000 mg/kg.28

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4.6 Hepatoprotective activity

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GL has been shown to significantly inhibit CCl4 induced liver damage at concentrations of 25–200 μg/ml. Alteration of the membrane fluidity by GL has been a theorized mechanism. GA presents hepatoprotective activity through lipid peroxidation and inhibiting free radicals.29 GL is effective in treating acetaminophen-induced hepatotoxicity.30

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4.7 Immunostimulatory activity

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In vitro studies showed that extracts of Glycyrrhiza glabra at 100μg/ml concentration improved the immune response. Production of TCD69 lymphocytes and macrophages from human granulocytes was significantly increased. Where in vivo studies showed that licorice root extract prevented the rise of immune-complexes related to autoimmune disorders.31

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5. Contraindications

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While Glycyrrhiza spp. has been recognized as generally safe for consumption, GA acts as an inhibitor of an enzyme which metabolizes cortisol falsely increasing urinary cortisol levels while blood serum levels remain unchanged.32 GA has been found to be responsible for an exaggerated ACTH response which can lead to hypocalcemia, and pseudoaldosteronism (a condition mimicking hyperaldosteronism which leads to hypertension) due to the enzyme inhibition developing excess levels of cortisol in the kidneys.33 Due to this cascade of effects, individuals who are prone to low blood pressure should consult their doctors before using Glycyrrhiza spp. Many different medications are shown to have cross-interactions with Glycyrrhiza spp. and thus anyone on medications should consult their doctors before using this herb.

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6. Conclusion

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Glycyrrhiza spp. having been studied for its medicinal value as an herb comes to no surprise with herbal medicines being brought to the public’s attention once again. The therapeutic properties of Glycyrrhiza spp. span many areas of health and help in some severe cases where modern pharmaceuticals are lacking. Glycyrrhiza spp. has been shown to be active against antibiotic resistant strains of bacteria like MRSA while also yielding potential for a vast array of other pathogens as an antibiotic, antiviral, and an antifungal. This herb also shows great potential as a hepatoprotective agent, anti-ulcer, anti-inflammatory, and an immunostimulatory agent. Further research is needed to standardize dosages and to further validate current findings, especially in the area of in vivo studies. However, due to its extremely low toxicity, Glycyrrhiza spp. surely shows significant potential for the future of medicine.

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Abbreviations

GA- Glycyrrhetic Acid
GL- Glycyrrhizin
GLD- Glabradin
LCA- Licochalcone A
LTG- Liquiritigenin
MRSA-> Methicillin-resistant staphylococcus aureus
TCM- Traditional Chinese Medicine

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