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Licorice

  • Written by Shahrul
  • Updated on March 6, 2021


Plant Part Used

Root

Active Constituents

Triterpene glycosides (including glycyrrhizin, glycyrrhitic acid), polysaccharides, flavonoids (including liquiritin, isoliquiritin, glabrol, apigenin, quercetin) (43),(44),(53), coumarin derivatives, formononetin.(1),(2) [span class=alert]

This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Glycyrrhiza glabra originates from the Mediterranean and Middle East countries. It has been used medicinally and as a flavoring agent since the 500 B.C. Licorice is used to flavor a wide variety of candies, gum, tobacco products, and beverages. The glycyrrhizin constituent is responsible for sweet taste of licorice which is 50 times sweeter than sugar.(42)

In terms of human well-being, licorice has been used traditionally for many health conditions, including fatigue (in the case of adrenal insufficiency),(3) as an expectorant,(4) in GI distress (particularly of benefit in ulcers),(5),(6),(7) diabetes, hypertension, obesity, cough, asthma, and inflammatory conditions.(8),(9),(41),(42),(43) The Chinese traditionally have also used Glycyrrhiza uralensis as a medicinal agent.

Interactions and Depletions

Interactions

Depletions

Dosage Info

Dosage Range

250-500mg (standardized extract), 3 times a day
-OR-
15-30 drops of a liquid extract (1:4w/v), 3 times a day in favorite beverage.

DGL licorice: 250-500mg, 3 times a day; products should be chewed for optimal results.

Tea: One cup of hot water over one teaspoonful of herb after each meal. (10)

Most Common Dosage

250mg (standardized extract), 3 times a day
-OR-
15-30 drops of a liquid extract (1:4w/v), 3 times a day in favorite beverage.

DGL licorice: 250mg, 3 times a day; products should be chewed for optimal results.

Tea: One cup of hot water over one teaspoonful of herb after each meal.

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 12-20% glycyrrhizin per dose (also known as glycyrrhizic or glycyrrhizinic acid); DGL (deglycyrrhizinated licorice) standardized to no greater than 1-2% glycyrrhizin per dose. Licorice supplements can be purchased in two forms. Regular licorice products with a glycyrrhizin (also known as glycyrrhizic or glycyrrhizinic acid)content usually of 12-20%, and then deglycyrrhizinated licorice (DGL), with a glycyrrhizin content usually not greater than 1-2%. The DGL product is recommended for peptic ulcer disease (chewable only) and those individuals susceptible to cardiovascular diseases such as hypertension. The products with a higher glycyrrhizin content are used as expectorants and for adrenal stress.

Uses

Frequently Reported Uses

  • Expectorant In Coughs, Bronchial Complaints
  • Ulcers (DGL)
  • Hepatoprotective
  • Bacterial Infections
  • Adrenal Support

Other Reported Uses

  • Viral Infections
  • Inflammation
  • Antioxidat
  • Antigenotoxic/Antimutagenic

Toxicities & Precautions

Health Conditions

Based on pharmacology and animal studies, licorice should be used with caution in individuals with hypertension, (11) kidney, (12) or liver problems. (13)

Side Effects

Based on animal data and pharmacology, if a non-DGL form is taken, there is a risk of pseudohyperaldosteronism leading to increased blood pressure, potassium loss, weakness and edema.(14),(15),(16) It is safest to use a deglycyrrhizinated (DGL) form in peptic ulcer to avoid this potential effect. (17)

Pregnancy/ Breast Feeding

If pregnant or nursing, consult a physician before use.

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.

Pharmacology

Licorice root is reported to have a variety of pharmacologic activities. Licorice root has phytoestrogenic activity due to its isoflavone content (formononetin). (18) Because of the weak affinity for binding to estrogen receptors, estrogenic side effects are not seen. Licorice root has an interesting effect on cortisol. It reportedly counteracts the effects of cortisol by inhibiting adrenal and thymus atrophy, as well as by reducing cholesterol manufacturing. (19) Licorice root is claimed to inhibit antibody formation and support the stress response and the inflammatory response. (20) Licorice root reportedly inhibits inflammatory prostaglandin formation and leukotrienes by inhibiting the enzymes responsible for their metabolic activation and manufacture. (21) Another more recent addition to the possible mechanism of the constituent glycyrrhizin’s anti-inflammatory activity is due in part to its anti-thrombin action. (22)

Licorice root is reported to have antioxidant effects, which can be linked to its hepatoprotective capabilities. (23),(24),(25) Flavonoids from licorice have been reported to provide protection to hepatocytes exposed to carbon tetrachloride, and galactosamine. (26) The research suggests that the anti-lipid peroxidation effect of licorice is the central mechanism contributing to its protective action against carbon tetrachloride-induced hepatotoxicity. (27) Further results suggest that glycyrrhiza may inhibit the NF-kappaB binding activity in carbon tetrachloride and ethanol-induced chronic liver injury. (28) Also, glycyrrhiza may be used in commercial topical skin preparations against damage caused by free radical and reactive oxygen species (ROS). (46)

Evidence from human and animal laboratory studies have demonstrated that the constituent isoliquatirin apioside found in licorice has antigenotoxic activity. This constituent has been reported to destroy ROS that initiate carcinogenesis and mutagenesis through oxidative DNA damage. The compound isoliquaritin apioside has also been reported to exert a protective effect against H2N2 and 4-nitroquinoline-N-oxide induced damage of DNA in Escherichia coli strains and in human blood lymphocytes. (47)

Licorice also has mucolytic activity and is used as an expectorant. The component glycyrrhizin produces demulcent and expectorant effects by stimulation of tracheal mucous secretion, although the potential for side effects are increased. (29) Licorice roots also contain polysaccharides which have been reported to be immunostimulating (increases macrophoges in vitro). (30) Licorice may also stimulate interferon production in the body, which could support its antiviral activity. (31),(32) Reported in an in vitro study, the glycyrrhizin in licorice is reported to inactivate herpes simplex virus particles irreversibly.(33) Flavonoids found in licorice root have been reported to have antimicrobial activity. (34)

Licorice root has been reported to have antimicrobial and antiviral activity. A laboratory study found that a component of licorice called glabridin is effective against Mycobacterium tuberculosis.(51) Clinical trials have investigated glycyrrhizin’s activity in chronic viral hepatitis and human immunodeficiency virus (HIV) infections. Glycyrrhizin has also been reported to prevent the development of hepatic carcinoma from hepatitis C and have in vitro antiviral activity against severe acute respiratory syndrome (SARS) associated corona virus.(45),(49)

Deglycyrrhizinated (DGL) licorice has demulcent activity, having the ability to protect irritated mucous membranes. (35) In cases where the intestinal lining is inflamed, DGL licorice reportedly stimulates the production of mucus, and is used to reduce symptoms. (36) Most studies on the stomach ulcer have focused mainly on polysaccharides constituent which act as anti-adhesive against the bacterial docking process of Helicobacter pylori to human stomach tissue. This bacterium is one of the main causes of chronic infection to the stomach ulcer. (44)

When compared with cimetidine in several clinical studies, a proprietary DGL licorice product performed as effectively as the pharmaceutical counterpart. (37) , (38) Another study reported in a double blind, placebo controlled crossover study that when DGL licorice was combined with aspirin, there was less blood loss in patients receiving the combination versus aspirin alone. (39)

The combination of licorice with other Korean native herbs including Lonicera japonica, Cassia obtusifolia L.,Adenophora triphylla var. japonica and Rhynchosia nulubilis has been reported to inhibit xanthine oxidase (XO) activity. Inhibition of XO can block the synthesis of uric acid, leading to the ability to treat gout and hyperuricemia. (40)

The polysaccharides of glycyrrhiza plants have been reported to have immune modulating activity in  laboratory animals. Laboratory studies have also reported that a high-fat diet decreased the proliferation index of spleen lymphocytes and the level of serum LgA, LgG and LgM in mice, therefore modulating immunostimulatory activity. When extract of polysaccharides were injected into mice, the level of immunostimulatory activity was increased by enhancing the level of serum LgA, LgG and LgM in mice. (48) Another study has reported the polysaccharide fraction has many functions including anti-viral and anti-tumor with a low cellular toxicity. (50)

Of note, licorice has been reported to have antidepressant activity in animal studies, possibly through the inhibition of monoamine oxidase by glycyrrhizin, which will increase the levels of monoamine such as epinephrine and dopamine in brain and subsequently lead to production of antidepressant effects. The results reported that licorice extract significantly reduced the immobility time of mice without any significant effect on its locomotor activity.(52)

References

  1. Hatano T, et al. Phenolic Constituents of Licorice. III. Structures of Glicoricone and Licofuranone, and Inhibitory Effects of Licorice Constituents on Monoamine Oxidase. Clin Pharm Bull. 1988;36:2090-97.
  2. Mahram GH, et al. A Further Contribution to the Triterpenoid Constituents of Glycyrrhiza glabra. Planta Medica. 1989;55:629.
  3. View Abstract: Gibson MR. Glycyrrhiza in Old and New Perspectives. Lloydia. 1978;41(4):348-54.
  4. Bradley PR, ed. British Herbal Compendium. Dorset, England: Bournemouth; 1992:145-48.
  5. Wilson JA. A Comparison of Carbenoxolone Sodium and Deglycyrrhizinated Liquorice in the Treatment of Gastric Ulcer in the Ambulant Patient. Br J Clin Pract. 1972;26:563-66.
  6. View Abstract: Van Marle J, et al. Deglycyrrhizinated Liquorice (DGL) and the Renewal of Rat Stomach Epithelium. European Journal of Pharmacology. 1981;72:219-25.
  7. View Abstract: Morgan AG, et al. Comparison between Cimetidin and Caved-S in the Treatment of Gastric Laceration, and Subsequent Maintenance Therapy. Gut. 1982;23:545-51.
  8. Tangri KK, et al. Biochemical Study of Anti-inflammatory and Anti-arthritic Properties of Glycyrrhetic Acid. Biochemical Pharmacology. 1965;14:1277-81.
  9. View Abstract: Akamatsu H, et al. Mechanism of Anti-inflammatory Action of Glycyrrhizin: Effect on Neutrophil Functions Including Reactive Oxygen Species Generation. Planta Medica. 1991;57:119-21.
  10. PDR for Herbal Medicines, 2nd ed. Montvale, NJ: Medical Economics Company; 2000:473.
  11. View Abstract: Folkersen L. Licorice. A basis for precautions one more time! Ugeskr Laeger. Dec1996;158(51):7420-1.
  12. View Abstract: Folkersen L. Licorice. A basis for precautions one more time! Ugeskr Laeger. Dec1996;158(51):7420-1.
  13. PDR for Herbal Medicines, 2nd ed. Montvale, NJ: Medical Economics Company; 2000:473.
  14. View Abstract: Epstein MT, et al. Effect of Eating Liquorice on the Renin-angiotensin-aldosterone Axis in Normal Subjects. Br Med J. 1977;1:488-90.
  15. View Abstract: Takeda R, et al. Prolonged Pseudoaldosteronism Induced by Glycyrrhizin. Endocrinology Japan. 1979;26(5):541-47.
  16. Farese RV, et al. Licorice-induced Hypermineralocorticoidism. New England J Med. 1991;325:1223-27.
  17. Glick L. Deglycyrrhizinated Liquorice for Peptic Ulcer. Lancet. 1982;2(8302):817.
  18. Kumagai A, et al. Effect of Glycyrrhizin on Estrogen Action. Endocrin Jpn. 1967;14(1):34-38.
  19. View Abstract: MacKenzie MA, et al. The Influence of Glycyrrhetinic Acid on Plasma Cortisol and Cortisone in Healthy Young Volunteers. J Clin Endocrin Metab. 1990;70:1637-43.
  20. View Abstract: Akamatsu H, et al. Mechanism of Anti-inflammatory Action of Glycyrrhizin: Effect on Neutrophil Functions Including Reactive Oxygen Species Generation. Planta Medica. 1991;57:119-21.
  21. Kimura Y, et al. Effects of Chalcones Isolated from Licorice Roots on Leukotriene Biosynthesis in Human Polymorphonuclear Neutrophils. Phytotherapy Res. 1988;2:140-45.
  22. View Abstract: Francischetti IM, et al. Identification of Glycyrrhizin as a Thrombin Inhibitor. Biochem Biophys Res Commun. Jun1997;235(1):259-63.
  23. View Abstract: Luper S. A Review of Plants Used in the Treatment of Liver Disease: Part Two. Altern Med Rev. Jun1999;4(3):178-88.
  24. View Abstract: Konovalova GG, et al. Antioxidant Activity of Parapharmaceutics Containing Natural Inhibitors of Free Radical Processes. Bull Exp Biol Med. Jul2000;130(7):658-60.
  25. View Abstract: Haraguchi H, et al. Protection of Mitochondrial functions against oxidative stresses by isoflavans from Glycyrrhiza glabra. J Pharm Pharmacol. Feb2000;52(2):219-23.
  26. Kiso Y, et al. Mechanism of Antihepatotoxic Activity of Glycyrrhizin. I: Effect on Free Radical Generation and Lipid Peroxidation. Planta Med. Aug1984;50(4):298-302.
  27. Kiso Y, et al. Mechanism of Antihepatotoxic Activity of Glycyrrhizin. I: Effect on Free Radical Generation and Lipid Peroxidation. Planta Med. Aug1984;50(4):298-302.
  28. View Abstract: Wang JY, et al. Inhibitory Effect of Glycyrrhizin on NF-kappaB Binding Activity in CCl4- Plus Ethanol-induced Liver Cirrhosis in Rats. Liver. Jun1998;18(3):180-5.
  29. Bradley PR, ed. British Herbal Compendium. Dorset, England: Bournemouth; 1992:145-48.
  30. View Abstract: Nose M, et al. Activation of Macrophages by Crude Polysaccharide Fractions Obtained from Shoots of Glycyrrhiza glabra and Hairy Roots of Glycyrrhiza uralensis In Vitro. Biol Pharm Bull. Oct1998;21(10):1110-2.
  31. View Abstract: Shinada M, et al. Enhancement of Interferon-gamma Production in Glycyrrhizin-Treated Human Peripheral Lymphocytes in Response to Concanavalin A and to Surface Antigen of Hepatitis B Virus. Proc Soc Exp Biol Med. 1986;181(2):205-10.
  32. Abe N, et al. Interferon Induction by Glycyrrhizin and Glycyrrhetinic Acid in Mice. Microbiol Immunol. 1982;26:535-39.
  33. View Abstract: Pompei R, Rlore O, Marccialis MA, et al. Glycyrrhizic Acid Inhibits Virus Growth and Inactivates Virus Particles. Nature. Oct1979;281(5733):689-90.
  34. View Abstract: Li W, Asada Y, Yoshikawa T. Antimicrobial Flavonoids from Glycyrrhiza glabra Hairy Root Cultures. Planta Med. Dec1998;64(8):746-7.
  35. View Abstract: Van Marle J, et al. Deglycyrrhizinated Liquorice (DGL) and the Renewal of Rat Stomach Epithelium. European Journal of Pharmacology. 1981;72:219-25.
  36. Wilson JAC. A Comparison of Carbenoxolone Sodium and Deglycyrrhizinated Liquorice in the Treatment of Gastric Ulcer in the Ambulant Patient. British Journal of Clinical Practice. 1972;26:563-66.
  37. D’Imperio N, et al. Double-blind Trial in Duodenal and Gastric Ulcers. Acta Gastro-Enterologica Belgica. 1978;41:427-34.
  38. View Abstract: Morgan AG, et al. Comparison Between Cimetidine and Caved-S in the Treatment of Gastric Ulceration, and Subsequent Maintenance Therapy. Gut. 1982;23:545-51.
  39. View Abstract: Rees WD, et al. Effect of Deglycyrrhizinated Liquorice on Gastric Mucosal Damage by Aspirin. Scandinavian J of Gastroenterology. 1979;14:605-07.
  40. Lee J., et al. Reparatory and preventive effects of oriental herb extract mixture (OHEM) on hyperuricemia and gout. Food Science and Biotechnology. April2010;2(19): 517-524
  41. Kuroda M.,et al. Phenolics from Glycyrrhiza glabra roots and their PPAR-γ ligand-binding activity. Bioorganic & Medicinal Chemistry. January2010;2(18): 962-970
  42. Khattak K. F., Simpson T. J. Effect of gamma irradiation on the antimicrobial and free radical scavenging activities of Glycyrrhiza glabra root. Radiation Physics and Chemistry. April 2010;4(79):507-512
  43. Cheel J., et al. Free radical-scavenging, antioxidant and immunostimulating effects of a licorice infusion (Glycyrrhiza glabra L.). Food Chemistry. October2010:3(122):508-517
  44. Wittschier N., Faller G., Hensel A. Aqueous extracts and polysaccharides from Liquorice roots (Glycyrrhiza glabra L.) inhibit adhesion of Helicobacter pylori to human gastric mucosa. Journal of Ethnopharmacology. Sept2009:218-223
  45. Talebpour Z., et al. Optimization of Microwave-Assisted Extraction for the Determination of Glycyrrhizin in Menthazin Herbal Drug by Experimental Design Methodology. Chromatographia. July2009;1-2(70):191–197
  46. Paola R.D., et al. Protective effects of glycyrrhizin in a gut hypoxia (ischemia)-reoxygenation (reperfusion) model. Intensive Care Medicine. April2009;4(35):687–697
  47. Kaur P., et al. Evaluation of antigenotoxic activity of isoliquiritin apioside from Glycyrrhiza glabra L. Toxicology in Vitro. June2009;4(23):680-686
  48. Hong Y., et al. Effects of Glycyrrhiza glabra polysaccharides on immune and antioxidant activities in high-fat mice. International Journal of Biological Macromolecules. July2009;1(45): 61-64
  49. Seki H., et al. Licorice β-amyrin 11-oxidase, a cytochrome P450 with a key role in the biosynthesis of the triterpene sweetener glycyrrhizin. Proc Natl Acad Sci U S A. Sept2008;37(105):14204–14209.
  50. RenJie L. Optimization of extraction process of Glycyrrhiza glabra polysaccharides by response surface methodology. Carbohydrate Polymers. Nov2008;4(74):858-861
  51. Gupta V. K., et al. Antimicrobial potential of Glycyrrhiza glabra roots. Journal of Ethnopharmacology. Mar2008;2(116):377-380
  52. Dhingra D., Sharma A. Antidepressant-like activity of Glycyrrhiza glabra L. in mouse models of immobility tests. Progress in Neuro-Psychopharmacology and Biological Psychiatry. May2006;3(30):449-454
  53. Singh B., et al. HPTLC Densitometric Quantification of Glycyrrhizin, Glycyrrhetinic Acid, Apigenin, Kaempferol and Quercetin from Glycyrrhiza glabra. Chromatographia. Dec2009;11-12(70):1665–1672

in this scope
Malaysian Herbal Monograph​
Medicinal Herbs & Plants Monographs​
Traditional Chinese Medicine Herbs (Professional Data)
Herbal Medicines Compendium (HMC) - U.S​

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