Disease relevance of GLYCYRRHETINIC ACID

• Glycyrrhetinic acid decreases plasma potassium concentrations in patients with anuria [1].
• Impact of dietary Na+ on glycyrrhetinic acid-like factors (kidney 11beta-(HSD2)-GALFs) in human essential hypertension [2].
• Inhibition of mutagenicity in Salmonella typhimurium and skin tumor initiating and tumor promoting activities in SENCAR mice by glycyrrhetinic acid: comparison of 18 alpha- and 18 beta-stereoisomers [3].
• CONCLUSIONS: The potent in vitro activity of GA against H. pylori provides a further explanation for its beneficial effect on peptic ulcers [4].
• OBJECTIVES: To investigate the in vitro activity of Extractum liquiritiae (EL), glycyrrhizic acid (GL), glycyrrhetinic acid (GA) and a novel lipophilic derivative of glycyrrhetinic acid monoglucuronide (GAMG), acetylated GAMG (aGAMG), against 29 Helicobacter pylori strains [4].

Psychiatry related information on GLYCYRRHETINIC ACID

• The inhibitory effect of 18beta-glycyrrhetol (Id) modified at the 30-position of glycyrrhetinic acid was weaker than that of glycyrrhetinic acid itself [5].

High impact information on GLYCYRRHETINIC ACID

• Transformed and untransformed cells were equally sensitive to inhibition of IJC by phorbol esters and by glycyrrhetinic acid, and also did not differ in the degree of upregulation of IJC by forskolin [6].
• Especially 18 alpha-oleanane derivatives having a CH2OH grouping converted from the COOH group initially allocated at C-17 were 100 times more effective than glycyrrhetinic acid both in vitro and in vivo [7].
• Proliferation assays showed that addition of glycyrrhetinic acid (an 11 beta-HSD2 inhibitor) resulted in a 30.3+/-7.7% inhibition of cell proliferation [8].
• Inhibition of GJIC of cells on EHS-matrix with 18 alpha glycyrrhetinic acid (GA) resulted in reversible downregulation of beta-casein expression [9].
• Glycyrrhetinic acid, a known inhibitor of the dehydrogenase reaction, also inhibited the reductase reaction at slightly higher concentrations (50% inhibitory concentration, less than 5 nM for dehydrogenase, 10-20 nM for reductase) [10].

Chemical compound and disease context of GLYCYRRHETINIC ACID

• This mechanism is related either to a mutation of the gene, which encodes 11HSD2 (apparent mineralocorticoid excess syndrome and some cases of low renin hypertension) or to an acquired reduction of the activity of the enzyme due to glycyrrhetinic acid, carbenoxolone, and grapefruit juice [11].
• Disodium glycyrrhetinic acid hemiphthalate (GAP) significantly inhibited the rat paw edema induced by carrageenin (ID50 = 21.37 mg/kg), and mice writhing responses caused by acetic acid (ID50 = 9.12 mg/kg) [12].
• Inhibitory effect of glycyrrhetinic acid derivatives on capsaicin-induced ear edema in mice [13].
• Different responsiveness in body weight and hepatic 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 mrna to 11beta-HSD inhibition by glycyrrhetinic acid treatment in obese and lean zucker rats [14].
• Glycyrrhetinic acid (GA), a free radical scavenger, protected gel entrapped hepatocytes from tacrine toxicity, but was ineffective in hepatocyte monolayers [15].

Biological context of GLYCYRRHETINIC ACID

• Others have shown that glycyrrhetinic acid apparently binds to a single proteinatious binding site in the plasma membrane [16].
• The isoflavonoid genistein, the cyclic triterpene glycyrrhetinic acid, and salicylate induce mitochondrial swelling and loss of membrane potential (DeltaPsi) in rat liver mitochondria (RLM) [17].
• Studies of pure astrocyte cultures and microscope analyses of neurons in mixed cultures showed that the increased oxidative stress and cell death in GA-treated cultures occurred only in neurons and not in astrocytes [18].
• A very weak cross-reaction with glycyrrhetinic acid monoglucuronide and glycyrrhetic acid occurred [19].
• We have previously demonstrated that cortisol-induced cutaneous vasoconstriction in man is potentiated by the 11 beta-OHSD inhibitor glycyrrhetinic acid, suggesting that 11 beta-OHSD may protect vascular corticosteroid receptors [20].

Anatomical context of GLYCYRRHETINIC ACID

• Evidence that disruption of connexon particle arrangements in gap junction plaques is associated with inhibition of gap junctional communication by a glycyrrhetinic acid derivative [16].
• Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22(phox) in human mononuclear leukocytes [21].
• Cultured rat kidney epithelial cells (NRK 52-E) expressed 11 beta HSD activity, which was inhibited by the licorice derivative glycyrrhetinic acid (GE) [22].
• Whether the mineralocorticoid effect of glycyrrhetinic acid is mediated by the adrenal glands or is due to a direct action on the renal tubule remains controversial [23].
• Thus, compound GM2296, a carbon-fucosylated derivative of glycyrrhetinic acid, inhibits E-, L-, and P-selectin-dependent eosinophil and neutrophil adhesion [24].

Associations of GLYCYRRHETINIC ACID with other chemical compounds

• Carbenoxolone (Cbx), a derivative of glycyrrhetinic acid, which has been found to affect mineralocorticoid and glucocorticoid receptors, induces swelling and membrane potential collapse when added to Ca(2+)-loaded liver mitochondria at 10 microM concentrations [25].
• Cortisone (500 nM) was as effective as 500 nM cortisol in inducing ASC differentiation, but this stimulatory effect was inhibited by coincubation with the 11betaHSD1 inhibitor, glycyrrhetinic acid [26].
• In the presence of glycyrrhetinic acid, an inhibitor of 11 beta-hydroxysteroid dehydrogenase, a high concentration of corticosterone (10 microM) did produce a slight inhibition of ACTH release [27].
• When prednisolone was injected together with glycyrrhetinic acid, an inhibitor of the 11 beta-OHSD, the ratios of prednisolone/prednisone in plasma and all tissues increased more than 10-fold [28].
• In this study, the effects of gap junction blockers 18 alpha-glycyrrhetinic acid (GRA) and carbenoxolone (CBX) have been compared with those of oleanolic acid (OLA) and glycyrrhizic acid (GZA), GRA analogs with no blocking effects [29].

Gene context of GLYCYRRHETINIC ACID

• DESIGN: Six healthy male subjects established in sodium balance were given either glycyrrhetinic acid (170 mg t.d.s., to inhibit 11 beta-HSD2), carbenoxolone (100 mg t.d.s., to inhibit both 11 beta-HSD1 and 11 beta- HSD2) or both inhibitors in combination [30].
• To address the relationship between bone morphogenetic protein (BMP) signaling and gap junction-mediated intercellular communication, we examined the effects of BMP-2 and a gap junction blocker 18 alpha glycyrrhetinic acid (18alpha-GCA) on mesenchymal cell condensation and chondrogenic differentiation in an in vitro chondrogenic model [31].
• Glycyrrhetinic acid abolished glucocorticoid metabolism and inhibited cell growth by 40%, the latter at concentrations consistent with glucocorticoid receptor (GR) and MR binding studies [32].
• These phosphorylations are selectively inhibited by CK-II inhibitors, such as quercetin, oGA (a glycyrrhetinic acid derivative) and NCS-chrom (an enediyne containing antibiotic) [33].
• Reduction or loss of pulmonary 11beta-HSD1 activity in glycyrrhetinic acid-treated rats substantially impaired foetal lung maturation (Hundertmark et al., Horm Metab Res, this issue) [34].

Analytical, diagnostic and therapeutic context of GLYCYRRHETINIC ACID

• 6. Glycyrrhetinic acid (Ia) and deoxoglycyrrhetol (IIa), the parent compounds, produced little inhibition by oral administration at less than 200 mg kg-1 [35].
• Determination of glycyrrhetinic acid in human plasma by high-performance liquid chromatography [36].
• Dermal patch anaesthesia for venous cannulation with 10% lignocaine gel containing glycyrrhetinic acid monohemiphthalate disodium as an absorption promoter [37].
• The anti-inflammatory and anti-nociceptive effects of disodium glycyrrhetinic acid hemiphthalate (glycyrrhetinic acid 3 beta-O-hemiphthalate sodium) after parenteral administration were determined in several animal models [12].
• Glycyrrhetinic acid (GA; 1) is one of the major constituents of a traditional Chinese medicine, the roots of Glycyrrhiza uralensis, called Gancao in Chinese. In the present paper, the biotransformation of GA by Mucor polymorphosporus (AS 3.3443) was investigated and eight metabolites were obtained [38].

References