Licorice

What Is Licorice?

Licorice is a popular herb with a few unique characteristics. In Chinese medicine, licorice is one of the premier tonic herbs and is found in a wide range of diverse herbal formulas for treating conditions ranging from depression and anxiety to infection and inflammation.

Licorice is an adrenal tonic that works by inhibiting the enzyme that breaks down cortisol. As a result, cortisol levels can be increased, which is useful for restoring function to fatigued adrenals, but can cause blood pressure to spike.

Licorice is also a popular herb for gastric and duodenal ulcers, to which there has been a good deal of research.

What Is Licorice Used For?

Licorice is mainly used for treating ulcers, digestive and respiratory tract inflammation, rheumatoid arthritis, diabetes, and metabolic syndrome. The corticosteroid mimicking activity of licorice makes it useful for treating conditions involving adrenal insufficiency and weaning off corticosteroid medications.

Traditional Uses

Licorice is one of the fundamental herbs used in traditional Chinese, Ayurvedic, and Kampo medicine.

In traditional Chinese medicine, licorice (known as Gan Cao), is used in two main forms; raw and prepared (usually by frying in honey).

Raw licorice is used to drain heat, reduce swelling, and detoxify. It’s considered to be a muscle relaxant, alleviates pain, and harmonizes the harsh actions of other herbs in the formula. It’s a common addition to a wide range of herbal formulas in traditional Chinese medicine for this reason. ^{11Reference 11Dafang Zeng · 2003Essentials Of Chinese Medicine Materia Medica}.

The saponin glycyrrhizin is intensely sweet. The Greek word Glycyrrhiza actually means sweet root.

Culpepper lists licorice as being useful for dry coughs, hoarseness of the throat, wheezing and shortness of breath.

Botanical Information

Licorice is a member of the Fabaceae (Leguminosae) family — the legume family, and the third largest family of flowering plants after Orchidaceae and Asteraceae, with 751 genera and around 19,000 species. Other members include soy, peanuts, and astragalus.

It’s a perennial herb, growing up to 150 cm tall. The rhizome is thick, red-brown colored on the outside, and yellowish on the inside.

The flowers of Glycyrrhiza glabra are zygomorphic.

Habitat, Ecology & Distribution

Licorice’s native range is from the Mediterranean to central and Southeast Asia.

Pharmacology & Medical Research

Antiacetylcholinesterase

Licorice powder (Glycyrrhiza glabra) (aqueous extract) (150 mg/kg), was shown to have a greater anti-acetylcholinesterase activity (25% inhibition), than nutmeg (Myristica fragrans) (15%) (5mg/kg), and Metrifonate (20% inhibition) (50 mg/kg) ^{3Reference 3Sigurjonsdottir et al. · 2003Subjects with essential hypertension are more sensitive to the inhibition of 11 β-HSD by liquorice}.

Effects On Cortisol

Some of the components of Glycyrrhiza glabra such as glycyrrhetinic acid have been shown to inhibit 11β-hydroxysteroid dehydrogenase, which is the enzyme responsible for the breakdown and metabolism of cortisol. This activity was noted to sustain 2 weeks after treatment was ceased. The renin-aldosterone system remained low for 6 months following treatment. ^{12Reference 12Farese Jr et al. · 1991Licorice-induced hypermineralocorticoidism}.

11β-hydroxysteroid dehydrogenase bidirectionally converts inactive cortisone to cortisol, especially in tissues high in enzyme activity such as fatty tissue and the liver ^{13Reference 13Stewart et al. · 2009Selective Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 for Patients With Metabolic Syndrome}.

Ulcers

The antiulcer effects of licorice were shown to be due mainly to the glycyrrhetinic acid content of the root, which is the aglycone of triterpenoid saponin glycoside glycyrrhizic acid (Mills, S., & Bone, K. 1999, pg. 746-747). The mechanism of action is suggested to be through prostaglandin mediation. Specifically through the inhibition of 15-hydroxyprostaglandin dehydrogenase and delta-13-prostaglandin reductase (Wan & Gottfried., 1985). This causes an increase in the associated prostaglandins, which trigger an increase in mucous secretion and cell proliferation in the stomach (Baker., 1994). This research was assisted by the creation of an identical semi-synthetic derivative of glycyrrhetinic acid and its glycoside precursor glycyrrhizic acid known commercially as Carbenoxolone (Mills & Bone, 1999).

Additionally, licorice extracts and semi-synthetic derivatives have been shown to produce anti pepsin activity in the stomach (Goso, Ogata, Ishihara, & Hotta., 1996), further improving the treatment of ulcers in the stomach.

Licorice was also shown to be effective in eradicating Helicobacter pylori in the treatment of peptic ulcer disease (PUD) (Momeni, Rahimian, Kiasi, Amiri, & Kheiri, 2014), though the study didn’t specify the extract used. The mechanisms of action are suggested to be through the flavonoid and polysaccharide fractions of Glycyrrhiza glabra extracts by inhibiting the adhesion of H. pylori to stomach tissue in vitro (human) (Wittschier, Faller, Beikler, Stratmann, & Hensel, 2006; Wittschier, Faller, & Hensel., 2009).

Deglycyrrhizinated licorice was found ineffective in the treatment of ulcers in a randomized clinical trial, further suggesting that the anti-ulcerative effects of licorice are reliant on the glycyrrhizin component (and associated saccharides and aglycones) (Bardhan, Cumberland, Dixon, & Holdsworth. 1978).

Serotonin Reuptake Inhibition

In a study investigating the effectiveness of licorice root extracts on serotonin reuptake inhibition as a way to analyze the possible antidepressant actions of the herb, serotonin reuptake was found to be effectively inhibited. The active constituents were found to be isoflavans and isoflavene constituents of licorice root. Glabridin inhibited serotonin reuptake in a dose-dependent manner similarly to the human hormone, estradiol. ^{2Reference 2Ofir et al. · 2003Inhibition of serotonin re-uptake by licorice constituentsView study →}.

Other constituents previously thought to have SSRI activity such as the isoflavone genistein and daidzein were instead found to be virtually inactive. ^{2Reference 2Ofir et al. · 2003Inhibition of serotonin re-uptake by licorice constituentsView study →}.

Phytochemistry

The defining constituent of licorice is the triterpenoid saponin glycyrrhizin (its acid form glycyrrhizic acid) — both the source of the root’s intense sweetness and of its most dangerous side effect. Its aglycone, glycyrrhetinic acid, drives the anti-ulcer activity. The flavonoid fraction is led by liquiritin and the chalcone isoliquiritin, while the prenylated isoflavane glabridin accounts for much of the antioxidant and serotonergic activity ^{1,2,3,4,5,6,7,8,9,10Reference 1Mazzio et al. · 2013High throughput screening to identify natural human monoamine oxidase B inhibitorsReference 2Ofir et al. · 2003Inhibition of serotonin re-uptake by licorice constituentsView study →Reference 3Sigurjonsdottir et al. · 2003Subjects with essential hypertension are more sensitive to the inhibition of 11 β-HSD by liquoriceReference 4Heilmann et al. · 1999Administration of glycyrrhetinic acid: significant correlation between serum levels and the cortisol/cortisone-ratio in serum and urineReference 5Krähenbühl et al. · 1994Kinetics and dynamics of orally administered 18 beta-glycyrrhetinic acid in humansReference 6Whorwood et al. · 1993Licorice inhibits 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone actionReference 7Sticher et al. · 1978Glycyrrhizinsaurebestimmung in Radix liquirtiae mit Hochleistungs Flussigkeitschromatographie (HPLC)Reference 8Wagner et al. · 1996Plant drug analysis: a thin layer chromatography atlasReference 9Bisset · 1994Herbal drugs and phytopharmaceuticals: a handbook for practice on a scientific basisReference 10Asl et al. · 2008ReviewReview of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds}.

MAO-B inhibitory components are reported to be due to the licopyranocoumarin licocoumarone and glycyrrhisoflavone content of Glycyrrhiza glabra ^{1Reference 1Mazzio et al. · 2013High throughput screening to identify natural human monoamine oxidase B inhibitors}.

The triterpenoid saponin glycyrrhizin (2-6% ^{7Reference 7Sticher et al. · 1978Glycyrrhizinsaurebestimmung in Radix liquirtiae mit Hochleistungs Flussigkeitschromatographie (HPLC)}) and its glycoside glycyrrhizic acid is both the cause of licorice’s most dangerous side effects and the active constituent for its biological activity. The main action of glycyrrhizin past its intense sweetness involves the inhibition of the enzyme 11-beta-hydroxysteroid dehydrogenase, which is responsible for metabolizing the stress hormone cortisol into the inactive form cortisone ^{4,5,6Reference 4Heilmann et al. · 1999Administration of glycyrrhetinic acid: significant correlation between serum levels and the cortisol/cortisone-ratio in serum and urineReference 5Krähenbühl et al. · 1994Kinetics and dynamics of orally administered 18 beta-glycyrrhetinic acid in humansReference 6Whorwood et al. · 1993Licorice inhibits 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone action}. This is beneficial for conditions involving adrenal insufficiency, glaucoma, osteopenia, and metabolic syndrome, but can also cause undesired side effects including hypertension, and fluid retention. Because of this, de-glycyrrhizinate versions of licorice extracts are commercially available.

Glycyrrhetinic acid is the aglycone of glycyrrhizic acid, which is considered the active constituent for licorice’s anti-ulcer activity through the mediation of prostaglandins in the mucous membrane.

The root also contains a wide range of flavonoids (1%-1.5%) which are responsible for the yellow color of the root. Flavones (including liquiritin, rhamnoliquiritin), chalcones (including isoliquiritin), isoflavonoids (including glabridin, glabrone, and formononetin). Also included are coumarins, fatty acids (C2 to C16), phenolic compounds, and arabinogalactans ^{8,9,10Reference 8Wagner et al. · 1996Plant drug analysis: a thin layer chromatography atlasReference 9Bisset · 1994Herbal drugs and phytopharmaceuticals: a handbook for practice on a scientific basisReference 10Asl et al. · 2008ReviewReview of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds}.

Constituent Summary

Figures are % of dried root; glycyrrhizin and glabridin levels vary widely with species (G. glabra vs. G. uralensis/G. inflata), origin, and extraction ^{7,8,10,14Reference 7Sticher et al. · 1978Glycyrrhizinsaurebestimmung in Radix liquirtiae mit Hochleistungs Flussigkeitschromatographie (HPLC)Reference 8Wagner et al. · 1996Plant drug analysis: a thin layer chromatography atlasReference 10Asl et al. · 2008ReviewReview of pharmacological effects of Glycyrrhiza sp. and its bioactive compoundsReference 14Simmler et al. · 2013Phytochemistry and biological properties of glabridin}.

Clinical Applications

Licorice is one of the main adrenal tonics available in herbal medicine (the other is rehmannia). It’s used alongside periods of adrenal fatigue to increase cortisol levels by inhibiting its breakdown.

Licorice is also especially useful for treating gastric and duodenal ulcers. In a similar effect, licorice is useful for soothing an inflamed gastrointestinal and respiratory tract.

The serotonin re-uptake inhibition attributed to the plant gives an explanation for the traditional antidepressant use of the herb. In clinical practice, this is a good addition to antidepressant formulas, but may not be potent enough to be used on its own.

Cautions & Safety

Do not use licorice with hypertensive individuals. Cortisol increases with licorice use can lead to a further heightened blood pressure.

References

1. Mazzio, E., Deiab, S., Park, K., & Soliman, K. F. A. (2013). High throughput screening to identify natural human monoamine oxidase B inhibitors. Phytotherapy Research, 27(6), 818-828.
2. Ofir, R., Tamir, S., Khatib, S., & Vaya, J. (2003). Inhibition of serotonin re-uptake by licorice constituents. Journal of Molecular Neuroscience, 20(2), 135-40. doi:http://dx.doi.org.ezproxy.laureate.net.au/10.1385/JMN:20:2:135
3. Sigurjonsdottir, H. A., Manhem, K., Axelson, M., & Wallerstedt, S. (2003). Subjects with essential hypertension are more sensitive to the inhibition of 11 β-HSD by liquorice. Journal of human hypertension, 17(2), 125-131.
4. Heilmann, P., Heide, J., Hundertmark, S., & Schöneshöfer, M. (1999). Administration of glycyrrhetinic acid: significant correlation between serum levels and the cortisol/cortisone-ratio in serum and urine. Experimental and clinical endocrinology & diabetes, 107(06), 370-378.
5. Krähenbühl, S., Hasler, F. E. L. I. X., Frey, B. M., Frey, F. J., Brenneisen, R. U. D. O. L. F., & Krapf, R. (1994). Kinetics and dynamics of orally administered 18 beta-glycyrrhetinic acid in humans. The Journal of Clinical Endocrinology & Metabolism, 78(3), 581-585.
6. Whorwood, C. B., Sheppard, M. C., & Stewart, P. M. (1993). Licorice inhibits 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone action. Endocrinology, 132(6), 2287-2292. Chicago
7. Sticher, O., & Soldati, F. (1978). Glycyrrhizinsaurebestimmung in Radix liquirtiae mit Hochleistungs Flussigkeitschromatographie (HPLC). Pharmaceutica acta Helvetiae.
8. Wagner, H., & Bladt, S. (1996). Plant drug analysis: a thin layer chromatography atlas. Springer Science & Business Media.
9. Bisset, N. G. (1994). Herbal drugs and phytopharmaceuticals: a handbook for practice on a scientific basis. Stuttgart: Medpharm Scientific Publishers xvi, 566p. ISBN 3887630254 En Originally published in German (1984).(EBBD, 190000550).
10. Asl, M. N., & Hosseinzadeh, H. (2008). Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytotherapy research, 22(6), 709-724.
11. Dafang Zeng. (2003). Essentials Of Chinese Medicine Materia Medica. Bridge Pub. Group. [traditional medical text].
12. Farese Jr, R. V., Biglieri, E. G., Shackleton, C. H., Irony, I., & Gomez-Fontes, R. (1991). Licorice-induced hypermineralocorticoidism. New England Journal of Medicine, 325(17), 1223-1227. [case study].
13. Stewart, P. M., & Tomlinson, J. W. (2009). Selective Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 for Patients With Metabolic Syndrome. Diabetes, 58(1), 14-15.
14. Simmler, C., Pauli, G. F., & Chen, S. N. (2013). Phytochemistry and biological properties of glabridin. Fitoterapia, 90, 160-184.