The roots and rhizomes of licorice (Glycyrrhiza) species have long been used worldwide as a herbal medicine and natural sweetener. Licorice root is a traditional medicine used mainly for the treatment of peptic ulcer, hepatitis C, and pulmonary and skin diseases, although clinical and experimental studies suggest that it has several other useful pharmacological properties such as antiinflammatory, antiviral, antimicrobial, antioxidative, anticancer activities, immunomodulatory, hepatoprotective and cardioprotective effects. A large number of components have been isolated from licorice, including triterpene saponins, flavonoids, isoflavonoids and chalcones, with glycyrrhizic acid normally being considered to be the main biologically active component. This review summarizes the phytochemical, pharmacological and pharmacokinetics data, together with the clinical and adverse effects of licorice and its bioactive components.

Review of Pharmacological Effects of Glycyrrhiza sp. and its Bioactive Compounds

Saponins occur widely in plant species and exhibit a range of biological properties, both beneficial and deleterious. This review, which covers the literature to mid 1986, is concerned with their occurrence in plants and their effects when consumed by animals and man. After a short discussion on the nature, occurrence, and biosynthesis of saponins, during which the distinction between steroidal and triterpenoid saponins is made, the structures of saponins which have been identified in a variety of plants used as human foods, animal feedingstuffs, herbs, and flavorings are described. Many of these compounds have been characterized only during the last 2 decades, and modern techniques of isolation, purification, and structural elucidation are discussed. Particular consideration is given to mild chemical and enzymatic methods of hydrolysis and to recent developments in the application of NMR and soft ionization MS techniques to structural elucidation. Methods currently used for the quantitative analysis of saponins, sapogenols, and glycoalkaloids are critically considered; advances in the use of newer methods being emphasized. The levels of saponins in a variety of foods and food plants are discussed in the context of the methods used and factors affecting these levels, including genetic origin, agronomic, and processing variables, are indicated. Critical consideration is given to the biological effects of saponins in food which are very varied and dependent upon both the amount and chemical structure of the individual compounds. The properties considered include membranolytic effects, toxic and fungitoxic effects, adverse effects on animal growth and performance, and the important hypocholesterolemic effect. A final section deals briefly with the pharmacological effects of saponins from ginseng, since use of this plant is increasing in certain sections of western society as well as being traditional in the Orient.

The chemistry and biological significance of saponins in foods and feedingstuffs.

Chemical analysis of the Chinese herbal medicine Gan-Cao (licorice)

Reversible inhibition of intercellular junctional communication by glycyrrhetinic acid.

Liquorice, Glycyrrhiza glabra L.—Composition, uses and analysis

Anti-inflammatory activity of the stereoisomers, 18 alpha and 18 beta-glycyrrhetinic acid (18 alpha and 18 beta-GA), obtained from Glycyrrhizae Radix, was investigated by using carrageenan-induced edema in mice and 18 alpha-GA was found to be more active than 18 beta-GA. Therefore, to clarify the difference of action of 18 alpha and 18 beta-GA, the inhibitory effects of both stereoisomers on the cotton pellet granuloma formation in adrenalectomized rats and on the reduction of steroidal compounds by delta 4-5 beta-reductase in the microsome fraction of rat liver were investigated. 18 alpha-GA, 30 mg/kg p.o., showed the similar antigranulomatous action in normal and adrenalectomized rats. On the other hand, 18 beta-GA, 30 mg/kg p.o., which exhibited the inhibitory effects in normal rats, showed no action in adrenalectomized rats. More than 50% of inhibitory effects of 18 alpha and 18 beta-GA on the 5 beta-reduction of testosterone and cortisol were recognized by an equimolar ratio of steroids to 18 alpha or 18 beta-GA. From these results, the activity of 18 alpha-GA is similar to that of glucocorticoid and the difference of action between 18 alpha-GA and 18 beta-GA could be explained by its stereochemical structure of D/E trans conformation. In addition to the glucocorticoid action, 18 alpha-GA inhibited the inactivation of endogenous glucocorticoid in liver, which is also recognized by the application of 18 beta-GA.

Comparative studies of the stereoisomers of glycyrrhetinic acid on anti-inflammatory activities

Separation and quantitative analysis of 18α-glycyrrhetinic acid and 18β-glycyrrhetinic acid in Glycyrrhizae Radix by gas/3-liquid chromatography

About 10 years ago, a protein family was shown for the first time to contain allergenic members, gibberellin-regulated protein (GRP). The first reported member was from peach, Pru p 7. One can hypothesize that it was not detected before because its physicochemical characteristics overlap with those of lipid transfer protein (LTP), a well-known allergen, or because the exposure to GRP increased due to an increase in the gibberellin phythormone level in plant food, either exogenous or endogenous. Like LTPs, GRPs are small cationic proteins with disulfide bridges, are resistant to heat and proteolytic cleavage, and are involved in the defense of the plant. Besides peach, GRP allergens have been described in Japanese apricot (Pru m 7), sweet cherry (Pru av 7), orange (Cit s 7), pomegranate (Pun g 7), bell pepper (Cap a 7), strawberry (Fra a GRP), and also in pollen with a restriction to Cupressaceae tree family (Cup s 7, Cry j 7, and Jun a 7). IgE cross-reactivities were described between GRPs, and the reported peach/cypress and citrus/cypress syndromes may therefore be explained because of these GRP cross-reactivities. GRPs are clinically relevant, and severe adverse reactions may sometimes occur in association with cofactors. More than 60% and up to 95% sequence identities are calculated between various allergenic GRPs, and three-dimensional models show a cleft in the molecule and predict at least three epitopic regions. The structure of the protein and its properties and the matrix effect in the original allergenic source should be unraveled to understand why, despite the ubiquity of the protein family in plants, only a few members are able to sensitize patients.

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Tatsuo Aizawa

Papers

Comparative studies of the stereoisomers of glycyrrhetinic acid on anti-inflammatory activities

Separation and quantitative analysis of 18α-glycyrrhetinic acid and 18β-glycyrrhetinic acid in Glycyrrhizae Radix by gas/3-liquid chromatography

Gibberellin-regulated proteins: Emergent allergens