Glycosides are compounds containing a carbohydrate and a noncarbohydrate residue in the same molecule.
The carbohydrate residue is attached by an acetal linkage at carbon atom 1 to a noncarbohydrate residue or AGLYCONE.
The nonsugar component is known as the AGLYCONE. The sugar component is called the GLYCONE.
If the carbohydrate portion is glucose, the resulting compound is a GLUCOSIDE.
An example is the methyl glucoside formed when a solution of glucose in boiling methyl alcohol is treated with 0.5% HCl as a catalyst.
The aglycone may be methyl alcohol, glycerol, a sterol, a phenol, etc. An acetal has two ether functions at a single carbon atom.
CLASSIFICATION OF GLYCOSIDES
When the chemical nature of the aglycone group is used as the basis of systematization, the classification is as follows:
Saponin glycosides are divided into 2 types based on the chemical structure of their aglycones (sapogenins). Saponins on hydrolysis yield an aglycone known as "sapogenin".
The so-called NEUTRAL saponins are derivatives of STEROIDS with spiroketal side chains. The ACID saponins possess triterpenoid structures.
The main pathway leading to both types of sapogenins is similar and involves the head-to-tail coupling of acetate units. However, a branch occurs, after the formation of the triterpenoid hydrocarbon, squalene, that leads to steroids in one direction and to cyclic triterpenoids in the other.
Glycyrrhiza is the dried rhizome and roots of Glycyrrhiza glabra. Glycyrrhiza contains:
1. A saponin glycoside called Glycyrrhizin (glycyrrhizinic acid).
Glycyrrhizin is the Ca2+ and K+ salts of glycyrrhizinic acid.
Glycyrrhizinic acid is 50 times sweeter than sugar (sucrose). Upon hydrolysis, the glycoside loses its sweet taste and is converted to the aglycone glycyrrhetinic acid plus two molecules of glucuronic acid.
Glycyrrhetinic acid is a pentacyclic triterpenoid derivative of the beta-amyrin type. It has expectorant and antitussive properties (Chandler,1985). Expectorants are used to decrease the viscosity of tenacious mucus, or to increase the secretion of mucus in dry irritant unproductive cough, thereby, lubricating the air passages and making coughing more productive. It is used considerably as a flavoring agent and is frequently employed to mask the taste of bitter drugs such as aloe, quinine etc.
Glycyrrhetinic acid inhibits the enzymes (15-hydroxyprostaglandin dehydrogenase & delta 13-prostaglandin) that metabolise the prostaglandins, PGE2 and PGF2alpha to their respective 15 keto-13,14-dihydro metabolites which are INACTIVE. This causes an increased level of prostaglandins in the digestive system. Prostaglandins inhibit gastric secretion but stimulate pancreatic secretion and mucous secretion in the intestines and markedly increase intestinal motility. They also cause cell proliferation in the stomach. The effect on gastric acid secretion, promotion of mucous secretion and cell proliferation shows why licorice has potential in treating peptic ulcer.
PGF2alpha stimulates activity of the uterus during pregnancy and can cause abortion, therefore, licorice should not be taken during pregnancy.
The structure of glycyrrhetinic acid is similar to that of cortisone. Both molecules are flat and similar at position 3 and 11.
This might be the basis for licorice's anti-inflammatory action.
3-Beta-D-(monoglucuronyl)18-beta-glycyrrhetinic acid, a metabolite of glycyrrhetinic acid inhibits 11-beta-hydroxysteroid dehydrogenase which converts ACTIVE cortisol to INACTIVE cortisone in the kidneys. The increased amounts of cortisol binds to the unprotected, unspecific mineralocorticoid receptors and induce sodium and fluid retention, hypokalaemia, hypertension and inhibition of the RENIN-ANGIOTENSIN-ALDOSTERONE system. Licorice should not be given to patients with a known history of high blood pressure. A prolonged usage of licorice can also cause the formation of cataracts.
Glycyrrhizin inhibits liver cell injury caused by many chemicals and is used in the treatment of chronic hepatitis and cirrhosis in Japan. It also inhibits the growth of several DNA and RNA viruses, inactivating herpes simplex virus particles irreversibly.
Georges-Louis Friedli, PgDip., MSc., PhD.
Benediktsson, R. and Edwards, C.R. (1994)Apparent mineralocorticoid excess. J. Hum. Hypertens. May;8(5):371-375.
Black, R. L., Oglesby, R. B., von Sallmann, L., and Bunim, J. L. (1960). Posterior subcapsular cataracts induced by corticosteroids in patients with rheumatoid arthritis. J.A.M.A.174: 166-171.
Chandler, R.F. (1985). Canadian Pharmaceutical Journal 118: 420-424.
Edwards, C.R., Benediktsson, R., Lindsay, R.S. and Seckl, J.R. (1996)11 beta-Hydroxysteroid dehydrogenases: key enzymes in determining tissue-specific glucocorticoid effects. Steroids Apr;61(4):263-269
Heikens, J., Fliers, E., Endert, E., Ackermans, M. and van Montfrans, G. (1995)Liquorice-induced hypertension--a new understanding of an old disease: case report and brief review. Neth. J. Med. Nov;47(5):230-234
Hikino, H. and Kiso, Y. Natural Products for Liver Diseases. "In Economic and Medicinal Plant Research. Vol.2, ed. H. Wagner, H. Hikino, and N. R. Farnsworth. Academic Press. London.1988.
Kato, H. Kanaoka, M. Yano, S. and Kobayashi, M. (1995)3-Monoglucuronyl-glycyrrhetinic acid is a major metabolite that causes licorice-induced pseudoaldosteronism. J. Clin. Endocrinol. Metab. Jun;80(6):1929-1933
Pompei, R. et al..(1980). Antiviral Activity of Glycyrrhizic Acid. Experientia 36 304-305.
Shimojo, M. and Stewart, P.M. (1995)Apparent mineralocorticoid excess syndromes. J. Endocrinol. Invest. Jul-Aug;18(7):518-532.
Sigurjonsdottir, H.A., Ragnarsson, J., Franzson, L. and Sigurdsson, G. (1995)Is blood pressure commonly raised by moderate consumption of liquorice? J. Hum. Hypertens. May;9(5):345-348.
Walker, B.R, Edwards, C.R. (1994)Licorice-induced hypertension and syndromes of apparent mineralocorticoid excess. Endocrinol. Metab. Clin. North Am. 1994 Jun;23(2):359-77 g