Disease relevance of GLYCYRRHETINIC ACID

• Habitual consumption of this compound may lead to hypertension and electrolyte disturbances due to inhibition of 11-beta-hydroxysteroid dehydrogenase by the metabolite glycyrrhetic acid [1].
• Purification and characterization of glycyrrhetic acid mono-glucuronide beta-D-glucuronidase in Eubacterium sp. GLH [2].
• The metabolite glycyrrhetic acid (GA) was produced by Eubacterium sp. GLH and Ruminococcus sp. PO1-3 in larger amounts and faster from GAMG than from GL [3].
• The phages which bound glycyrrhetic acid conjugated bovine serum albumin were enriched from this library using phage display technique as the pilot experiments [4].
• Eubacterium sp. GLH with Ruminococcus sp. PO1-3 and Clostridium innocuum ES24-06 possessing enzymes involved in the metabolism of glycyrrhizin (GL) was cultured in GAM medium with and without 1.0 mM GL or 1.0 mM glycyrrhetic acid (GA) [5].

High impact information on GLYCYRRHETINIC ACID

• RESULTS: After placebo or GRA, cortisol infusion did not change RVR, RBF or blood pressure [6].
• Enzyme-linked immunosorbent assay for glycyrrhizin using anti-glycyrrhizin monoclonal antibody and an eastern blotting technique for glucuronides of glycyrrhetic acid [7].
• Glycyrrhetic acid inhibited the increased phospholipid metabolism of cultured cells induced by tumor promoters, 12-O-tetradecanoylphorbol-13-acetate or teleocidin, and it markedly suppressed the promoting effect of teleocidin on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene [8].
• Because glycyrrhetic acid is a 200-1000 times more potent inhibitor of 11-beta-hydroxysteroid dehydrogenase compared to glycyrrhizic acid, the kinetics of glycyrrhetic acid are relevant in a toxicological perspective [9].
• After outflow of the bile into the duodenum, the conjugates are hydrolyzed to glycyrrhetic acid by commensal bacteria; glycyrrhetic acid is subsequently reabsorbed, causing a pronounced delay in the terminal plasma clearance [9].

Chemical compound and disease context of GLYCYRRHETINIC ACID

• Competition in the metabolism of glycyrrhizin with glycyrrhetic acid mono-glucuronide by mixed Eubacterium sp. GLH and Ruminococcus sp. PO1-3 [3].
• From these results the enzyme is defined as glycyrrhetinate dehydrogenase, being quite different from 3 beta-hydroxysteroid dehydrogenase of Ruminococcus sp. from human intestine, which is active for both glycyrrhetic acid and steroids having the 3 beta-hydroxyl group [10].

Biological context of GLYCYRRHETINIC ACID

• The effects of components of aqueous licorice root extract (LE) on the pharmacokinetics of glycyrrhizin (G) and glycyrrhetic acid (GA) were investigated in rats and humans [11].
• Although hepatic lysosomes from mouse and cattle hydrolysed GAMG to GA similarly to those from rat, the hydrolysis of GAMG was not detected in lysosomes of human and porcine livers [12].
• The results of kinetic analysis suggested that glycyrrhetic acid directly binds to the TPA receptor, resulting in the competitive inhibition of the binding of TPA to its receptor without affecting the number of binding sites (Ki = 2.2 X 10(-4) M) [13].
• The role of enterohepatic circulation of glycyrrhetic acid (GA) in rats was determined by kinetic analysis of GA [14].
• Glycyrrhetic acid suppressed tumor promoter-induced effects in vitro, such as stimulation of 32Pi-incorporation into phospholipids of cultured cells and down-regulation of the epidermal growth factor receptor [15].

Anatomical context of GLYCYRRHETINIC ACID

• GA was also produced slowly from GL after time lag by the lysosomes [12].
• Physiologically based pharmacokinetic modeling indicated that, in humans, the transit rate of gastrointestinal contents through the small and large intestines predominantly determines to what extent glycyrrhetic acid conjugates will be reabsorbed [9].
• The results indicated that pure GZ was hydrolyzed to GA more rapidly and to a greater extent than that in licorice decoction by various feces [16].
• Inhibition of 12-O-tetradecanoylphorbol-13-acetate-stimulated 3-O-methyl-glucose transport in mouse Swiss 3T3 fibroblasts by glycyrrhetic acid [17].
• The transcellular transport of [(3)H]digoxin across Caco-2 cell monolayers was then examined in the presence of (R)-(+)-citronellal, abietic acid, and glycyrrhetic acid [18].

Associations of GLYCYRRHETINIC ACID with other chemical compounds

• Rat liver lysosomes hydrolysed GAMG to 18 beta-glycyrrhetic acid (GA) at only 30% rate compared with the rate of GL to GAMG [12].
• Glycyrrhizic acid is hydrolysed in the intestine to the pharmacologically active compound glycyrrhetic acid, which inhibits the enzyme 11 beta-hydroxysteroid dehydrogenase (in the direction of cortisol to cortisone) as well as some other enzymes involved in the metabolism of corticosteroids [19].
• Direct determination of serum glycyrrhetic acid by a monoclonal antibody-based inhibition ELISA using ibuprofen for releasing serum albumin-bound glycyrrhetic acid [20].
• Co-administration of histamine H2-receptor antagonist (cimetidine) and anticholinergic drug (scopolamine butyl bromide) with SGT didn't influence the area under the plasma concentration-time curves (AUC) of glycyrrhetic acid (GA), an active metabolite derived from GL in SGT [21].

Gene context of GLYCYRRHETINIC ACID

• 18alpha,beta-Glycyrrhetic acid (GA) did not inhibit IL-8 but inhibited eotaxin 1 [22].
• Inhibitory effects of glycyrrhetic acid and its related compounds on 3 alpha-hydroxysteroid dehydrogenase of rat liver cytosol [23].
• Interestingly, compounds 14, 15, and 17 showed similar inhibitory effects (89-92%, 66-69%, and 24-29% at 1000, 500, and 100 mol ratio to TPA, respectively) against EBV-EA with potencies comparable to those of glycyrrhetic acid, a known natural antitumor-promoter [24].
• Glycyrrhizin (G) and glycyrrhetic acid (GA) were separated by using nano-liquid chromatography (nano-LC) in a fused silica capillary packed with RP18 stationary phase (75 microm ID, effective length 33 cm, packed 23 cm) eluting at 300 nL/min in a gradient mode [25].

Analytical, diagnostic and therapeutic context of GLYCYRRHETINIC ACID

• In the procedure, G and GA were detected in biological fluids by means of recently improved HPLC methods [11].
• This parameter, which can be estimated noninvasively, may serve as a useful risk estimator for glycyrrhizic-acid-induced adverse effects, because in subjects with prolonged gastrointestinal transit times, glycyrrhetic acid might accumulate after repeated intake [9].
• Determination of glycyrrhetic acid in human serum by high-performance liquid chromatography with ultraviolet detection [26].
• From a preliminary study in human volunteers, it was concluded that glycyrrhetic acid rather than glycyrrhizin is preferred in a study in human volunteers to assess the zero effect level of glycyrrhizin [27].
• Glycyrrhizin is one of the active glycosides in Gancao and SGT and is hydrolysed into the bioactive metabolite, 18 beta-glycyrrhetic acid (GA) by intestinal bacteria following oral administration [28].

References