The substance has a sweet taste, so it is used in flavoring to mask the bitter taste of drugs like aloe and quinine. It may have some anti-inflammatory activities.[1] One of its metabolites is responsible for the blood pressure-increasing effect of liquorice.[2]
Medical uses
Oral topical
In Turkey, enoxolone is used in a "Anzibel" lozenge in combination with benzocaine (a local anesthetic) and chlorhexidine HCl (an antibacterial).[3]
It is found in an over-the-counter "Arthrodont" toothpaste. Evidence for the ingredient's usefulness for plaque and gingivitis is lacking.[4]
Skin topical
In Japan, enoxolone is found in the "Salonpas" pain-relief menthol patch.[3]
It is also used in the Singaporean "Vetic" cream.[3] In the United States, it is found in PruClair, a "precription medical device" indicated for generic dermatoses.[5]
Possible other uses
Enoxolone is effective in the treatment of peptic ulcer and also has expectorant (antitussive) properties.[1] It has some additional pharmacological properties with possible antiviral, antifungal, antiprotozoal, and antibacterial activities.[6][7][8][9]
Mechanism of action
Anti-inflammatory
Glycyrrhetinic acid inhibits the enzymes (15-hydroxyprostaglandin dehydrogenase and delta-13-prostaglandin) that metabolize the prostaglandins PGE-2 and PGF-2α to their respective, inactive 15-keto-13,14-dihydro metabolites. This increases prostaglandins in the digestive system. Prostaglandins inhibit gastric secretion, 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, and promotion of mucous secretion and cell proliferation shows why licorice has potential in treating peptic ulcers.[10]
Licorice should not be taken during pregnancy, because PGF-2α stimulates activity of the uterus during pregnancy and can cause abortion.[citation needed]
The structure of glycyrrhetinic acid is similar to that of cortisone. Both molecules are flat and similar at positions 3 and 11. This might be the basis for licorice's anti-inflammatory action.[citation needed]
Hypertensive
3-β-D-(Monoglucuronyl)-18-β-glycyrrhetinic acid, a metabolite of glycyrrhetinic acid, inhibits the conversion of 'active' cortisol to 'inactive' cortisone in the kidneys.[11] This occurs via inhibition of the enzyme 11-β-hydroxysteroid dehydrogenase.[citation needed] As a result, cortisol levels become high within the collecting duct of the kidney. Cortisol has intrinsic mineralocorticoid properties (that is, it acts like aldosterone and increases sodium reabsorption) that work on ENaC channels in the collecting duct.[citation needed]Hypertension develops due to this mechanism of sodium retention. People often have high blood pressure with a low renin and low aldosterone blood level.[citation needed] The increased amounts of cortisol binds to the unprotected, nonspecific mineralocorticoid receptors and induce sodium and fluid retention, hypokalaemia, high blood pressure, and inhibition of the renin-angiotensin-aldosterone system. Therefore, licorice should not be given to patients with a known history of hypertension in doses sufficient to inhibit 11-β-hydroxysteroid dehydrogenase.[2]
Derivatives
Glycyrrhetinic acid derivatives, where R is a variable functional group
In glycyrrhetinic acid, the functional group (R) is a hydroxyl group. Research in 2005 demonstrated that with a proper functional group a very effective glycyrrhetinic artificial sweetener can be obtained.[12] When R is an anionic NHCO(CH2)CO2K side chain, the sweetening effect is found to be 1200 times that of sugar (human sensory panel data). A shorter or longer spacer reduces the sweetening effect. One explanation is that the taste bud cell receptor has 1.3 nanometers (13 angstroms) available for docking with the sweetener molecule. In addition, the sweetener molecule requires three proton donor positions, of which two reside at the extremities, to be able to interact efficiently with the receptor cavity.
A synthetic analog, carbenoxolone, was developed in Britain.[citation needed] Both glycyrrhetinic acid and carbenoxolone have a modulatory effect on neural signaling through gap junction channels.
^Badam L (June 1997). "In vitro antiviral activity of indigenous glycyrrhizin, licorice and glycyrrhizic acid (Sigma) on Japanese encephalitis virus". The Journal of Communicable Diseases. 29 (2): 91–99. PMID9282507.
^Fuji HY, Tian J, Luka C (1986). "Effect of glycyrrhetinic acid on influenza virus and pathogenic bacteria". Bull. Chin. Mater. Med. 11: 238–241.
^Guo N (October 1991). "[Protective effect of glycyrrhizine in mice with systemic Candida albicans infection and its mechanism]". Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae. 13 (5): 380–383. PMID1839259.
^Salari MH, Sohrabi N, Kadkhoda Z, Khalili MB (2003). "Antibacterial effects of Enoxolone on periodontopathogenic capnophilic bacteria isolated from specimens of periodontitis patients". Iranian Biomedical Journal. 7: 39–42.
^Kato H, Kanaoka M, Yano S, Kobayashi M (June 1995). "3-Monoglucuronyl-glycyrrhetinic acid is a major metabolite that causes licorice-induced pseudoaldosteronism". The Journal of Clinical Endocrinology and Metabolism. 80 (6): 1929–1933. doi:10.1210/jcem.80.6.7775643. PMID7775643.
