Licorice (Glycyrrhiza glabra)

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Licorice Summary

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.

 

+ Indications:

  • Adrenal Insufficiency
  • Adrenal insufficiency
  • Arthritis
  • Canker Sores
  • Chronic fatigue syndrome
  • Diabetes
  • Digestive tract inflammation
  • Endometriosis
  • Fibromyalgia
  • Gastric ulcer
  • Herpes Virus
  • Human Immunodefficiency Virus HIV
  • metabolic syndrome
  • Multiple Sclerosis
  • Respiratory tract inflammation
  • Systemic Lupus Erythematosus SLE
  • Ulcers
  • Weaning off corticosteroid medications

+ Contraindications:

  • Hypertension

Herbal Actions:

  • Nootropic
  • Anodyne
  • Antispasmodic
  • Antinflammatory
  • Emolient
  • Estrogenic
  • Expectorant
  • Anti-ulcer
 

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 of 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 is considered to be a muscle relaxant, alleviates pain, and harmonizes the harsh actions of other herbs in the formula. It is a common addition to a wide range of herbal formulas in traditional Chinese medicine for this reason. [11].

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.

 

Weekly Dose

Part Used

Root

Family Name

Leguminoseae

Distribution

Europe (Mediteranean)

Throughout Southeast Asia

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Constituents of Interest

  • Glycyrrhizin
  • Licopyranocoumarins
  • Glycyrrhisoflavone
  • Liquiritin
  • Formonetin

Common Names

  • Licorice
  • Sweet root
  • Gan Cao (China)
  • Kanzo (Japan)
  • Kamcho (Korea)
  • Subholzwurzel (Germany)
  • Lakritzenwurzel (Germany)
  • Reglisse
  • Bois Doux (France)
  • Liquirizia (Italy)
  • Lakrids (Danish)
  • Yashimadhu (Sanskrit)

CYP450

Unknown

Nature/Taste

Unknown

Pregnancy

Unknown

Duration of Use

  • Avoid long-term use in therapeutic doses.
 

Botanical Information

Licorice is a member of the Leguminoseae family of plants, which comprises 751 genera and 19,000 species, making it the third largest group of flowering plants only to Orchidaceae and Asteraceae.

Liquorice is part of the Fabaceae family of plants, which is more commonly known as the legume family. This includes such species as 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, and Distributio

Liquorice's native range is from the Mediterranean to central and Southeast Asia.

 

Pharmacology & Medical Diagnosis

+ Antiacetylcholinesterase

Licorice powder (Glycyrhiza glabra) (aqueouse extract) (150 mg/kg), was shown to have a greater anti-acetylcholinesterase activity (25% inhibition), than nutmeg (Myristica fragrens) (15%) (5mg/kg), and Metrifonate (20% inhibition) (50 mg/kg) [3].

+ 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. [12].

11β-hydroxysteroid dehydrogenase bidirectionally converts inactive cortisone to cortisol, especially in tissues high in enzyme activity such as fatty tissue and the liver [13].

This activity was noted to sustain 2 weeks after treatment was ceased. The renin-aldosterone system remained low for 6 months following treatment [12].

+ 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 an increase of 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 similarily to the human hormone, estradiol. [2].

Other constituents previously thought to have SSRI activity such as the isoflavone genistein and daidzein was instead found to be virtually inactive. [2].

 

Phytochemistry

MAO-B inhibitory components are reported to be due to the licopyranocoumarin licocoumarone and glycyrrhisoflavone content of Glycyrrhiza glabra [1].

The triterpenoid saponin glycyrrhizin (2-6% [7]) and it's glycoside glycyrrhizic acid is both the cause of licorices 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 [4-6]. 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.

Glycyrrhetinicc acid is the aglycone of glycyrrhizic acid, which is considered the active constituent for licorices 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 formonetin). Also included are coumarins, fatty acids (C2 to C16), phenolic compounds, and arabinogalactans. [8-10.

glycyrhetinic-acid.png
 

Clinical Applications Of Licorice:

Licorice is one of the main adrenal tonics available in herbal medicine (the other is rehmannia). It is 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 inflammed gastrointestinal and repiratory tract.

The serotonin reuptake inhibition attribiuted to the plant give 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:

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

 

Author

Justin Cooke, BHSc

The Sunlight Experiment

(Updated November 2018)

 

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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.