Licorice

(Glycyrrhiza Glabra)

Mike Darnofall and Stew Eckard

I. General Description

• Perennial, warm temperate zone (Old and New Worlds) herb or subshrub, 3-7 feet high, with light, spreading, pinnate foliage (feathery appearance) and spikes of small blue, violet, cream colored flowers.
• Genus Glycyrrhiza contains 14 species with G. Glabra being the chief source of the drug.
• Parts used are dried runners and roots, harvested in autumn of the third or fourth season.
• One of the most extensively used and scientifically investigated herbal products

II. Chemical Composition

• Major active component is glycyrrhizin (6-10%).
• Glycyrrhizin is cleaved by intestinal flora to glycyrrhetinic acid and a disaccharide.
• Deglycyrrhizinated licorice (DGL) is a licorice extract with the glycyrrhizin removed.
• Other important constituents include flavonoids, isoflavonoids, chalcones, coumarins, triterpenoids, sterols, starch (2-20%), sucrose and glucose (3-14%), lignins, amino acids, amines, gums, volatile oils.

III. History and Folk Use

• Use dates back several thousand years in both Western and Eastern cultures.
• Traditional uses: peptic ulcers, asthma, pharyngitis, malaria, abdominal pain, insomnia, infections.
• Also used as a vehicle for disguising taste of acrid / bitter medicines.
• Other uses: brewers add licorice to porter and stout beer to give thickness and blackness; black licorice is used in manufacture of tobacco.

IV. Pharmacology  (active compounds are glycyrrhizin, glycyrrhetinic acid, and flavonoids).

• Estrogenic activity

• 1. alterative action on estrogen metabolism.
• 2. estrogenic activity is due to its isoflavone content.
• 3. glycyrrhetinic acid antagonizes estrogens
• 4. experimental animal studies using crude licorice extract suggest estrogenic activity of isoflavones is more important than estrogen antagonism of glycyrrhetic acid.

• Pseudoaldosterone activity

• causes loss of potassium along with sodium and water retention, resulting in increased blood pressure.
• results from glycyrrhetinic acid inhibition of aldosterone breakdown by 5-beta-reductase in the liver.
• 5-beta reductase also responsible for inactivating cortisol and progesterone in addition to aldosterone.

• Antiinflammatory antiallergic activity

• 1. "cortisol-like-effects" plus antagonism of negative effects of cortisol (increased cholesterol synthesis, thymus atrophy, adrenal atrophy).
• 2."cortisol-like-effects" of licorice include: inhibition of antibody formation, inhibition of stress reaction and inflammation.
• 3. "cortisol-like-effects" of licorice are due to inhibition of cortisol degradation in the liver by 5-beta-reductase, and inhibition of phospholipase A2 (first step in the synthesis of inflammatory prostaglandins and leukotrienes).

• Immunostimulatory /antiviral effects

• 1. glycyrrhizin and glycyrrhetinic acid induce interferons.
• 2. interferons bind to cell surfaces, and stimulate synthesis of intracellular proteins that block viral DNA.
• 3. interferons also activate macrophages, and increase natural killer cell activity.
• 4. viruses inhibited include: vaccina, Newcastle disease, vesicular stomatitis, herpes simplex 1 (irreversible), HIV.

• Antibacterial activity

• alcohol extracts show in vitro activity against Staph aureus, Strep mitans, Mycobacterium smegmatis, Candida albicans.
• majority of effects are due to isoflavonoids.

• Antihepatotoxic activity

• inhibition of chemically-induced liver damage in animal studies.
• mechanism believed to be inhibition of free radical formation by NADPH-cytochrome P450 reductase.

V. Clinical Uses of Licorice

Oral

• Deglycyrrhinized licorice (DGL)

• peptic ulcers (most popular)
• canker sores

• Viral infections
• Inflammation
• Menstrual and menopausal disorders

Topical glycyrrhetinic acid

• Herpes
• Eczema
• Psoriasis

VI. Toxicity

• Aldosterone-like effects: sodium and water retention, potassium depletion, hypertension, suppression of the renin-aldosterone system.
• Doses of >3 grams/day for > 6 weeks (root), > 100 milligramslday (glycyrrhizin) are associated with toxicity.
• Adverse effects are rare at < 100 milligrams /day; common at > 400 milligrams /day.
• Prevention of ADR possible by following a high potassium/low sodium diet, monitoring blood pressure and electrolytes.

VII. Drug and Disease Interactions

• Drugs

• corticosteroids (increased effect)
• digitalis preparations (increased effect)
• estrogens/progesterone (altered effect)
• anti-hypertensives (decreased effect)

• Diseases

• 1. hypertension
• 2. renal failure
• 3. heart disease

VIII. Dosage

• Dosage for most clinical applications is based on the level of glycyrrhetinic acid.
• For peptic ulcer DGL is preferred because it works as well as glycyrrhetinic acid without side effects. DGL must mix with saliva to be effective.
• The following doses, TID, produce safe and effective glycyrrhetinic acid levels: I. powdered root; 1-2 grams 2. fluid extract (1:1); 24 milliliters 3. solid (dry powdered) extract (4:1); 250-500 milligrams

IX. Clinical Trials

• Peptic Ulcers

• DGL stimulates normal defense mechanisms (mucosal lining of the digestive tract) rather than reducing acidity (H2-antagonists).
• DGL shown to be as effective as H-2 antagonists / antacids in healing ulcers with fewer relapses and no significant side effects.
• DGL strongly indicated for the prevention of gastric ulcers in patients taking ulcerogenic drugs (aspirin, NSAIDS, corticosteroids).
• dose for DGL is 2-4 380 mg chewable tablets between or 20 minutes before meals.

• Hepatitis

• SNMC (0.2% glycyrrhizin, 0.1% cysteine, 2% glycine in normal saline,
• improved liver function in Hepatitis B and produced complete resolution in 40% of patients.

• HIV/AIDS

• 100-225 mg glycyrrhizin daily halted disease progression in 16 hemophiliac AIDS patients.
• 200-800 mg glycyrrhizin IV daily produced improvement in immune function (increased helper T cell counts, improved helper-to-suppressor T-cell ratios, improved liver function) in nine HIV positive patients.

• Eczema and Psoriasis

• topical glycyrrhetinic acid exerted an effect similar to hydrocortisone and may even be better.
• glycyrrhetinic acid also potentiated topical hydrocortisone by inhibiting its degradation.

X. Sources

1. Castleman, M. The Healing Herbs. Rodale Press, Emmaus, PA. 1991. Pp 236-240.

2. Eisenburg, J: Treatment of Chronic Hepatitis B: Effect of Glycyrrhizinic acid on the course of illness. Forschr Med 110, 395-398, 1992.

3. Evans, FQ: The rational use of glycyrrhetinic acid in dermatology. Br. J. Clin. Pract. 12, 269-279, 1958.

4. Grieve, M. A Modern Herbal (http://www.botanical.com).

5. Ikegami, N. et al.: Prophylactic effect of long-term oral administration of glycyrrhizin on AIDS development of asymptomatic patients. Int Conf AIDS 9(1), 234, 1993.

6. Kasser, Z.A.: Endoscopic controlled trial of four drug regimens in the treatment of chronic duodenal ulceration. Irish Med. J. 78, 153-156,1985.

7. Mori, K. et al.: The present status in prophylaxis and treatment of HIV infected patients with hemophilia in Japan. Rinsho Byhori 37(11), 1200-1208, 1989.

8. Murray, Pizorno. Encyclopedia of Natural Medicine. Prima Publishing. Rocklin, CA. 1991. Pp 67, 353-354, 498-499, 522-524, 531.

9. Murray, Pizzorno, The Textbook of Natural Medicine. Bastyr. Univ. Pub., 1996.

10. Ody, P. The Complete Medicinal Herbal. Dorling Kindersly, NY, NY. 1993. P65 .

11. Orchin, M. et al. The Vocabulary of Organic Chemistry. Wiley and Sons, NY, NY. 1980. P 478.

12. Rees WDW, et al.: Effect of DGL on gastric mucosal damage by aspirin. Scan. J. Gastroenterol 14, 605-607, 1979.

13. Stecher, P., ed. The Merck Index, Eighth Edition. Merck and Co., Rahway, N.J. 1968. Pp 30, 502.

14. Teelucksingh S., et al.: Potentiation of hydrocortisone activity in skin by glycyrrhetinic acid. Lancet 335, 1060-1063, 1990.