Disease relevance of enoxolone

• In the second series of experiments, three GJ blockers (heptanol, 18beta-glycyrrhetinic acid, and 2,3-butanedione monoxime) infused after the onset of ischemia reduced infarct size after 30-min ischemia/2-h reperfusion to an extent equivalent to that in the case of PC [1].
• Allergic contact dermatitis from enoxolone [2].
• Allergic contact dermatitis mimicking atopic dermatitis due to enoxolone in a topical medicament [3].

High impact information on enoxolone

• The purpose of this study was to evaluate the potential modulation by a primary component of licorice root, glycyrrhizin (GL), and its metabolite, 18beta-glycyrrhetinic acid (GA), in a hepatocyte model of cholestatic liver injury [4].
• IBOP reduced the passage of microinjected dyes between HEC by 50%, and the effects of IBOP on migration and tube formation were mimicked by the gap junction inhibitor 18beta-glycyrrhetinic acid (1 microM) with a similar time course and efficacy [5].
• Pretreatment with the GJIC blockers 18beta-glycyrrhetinic acid and oleamide did not affect the changes induced by Cx26 transfection [6].
• To investigate the function of gap junctions in the development of the lens, we have examined the effect of the gap junction blocker 18beta-glycyrrhetinic acid (betaGA) on the differentiation of primary cultures (both dissociated cell-derived monolayers and central epithelium explants) of embryonic chick lens epithelial cells [7].
• Thus, 18beta-glycyrrhetinic acid may be useful in studying the function of both arteriolar smooth muscle and endothelial cells while they remain located within a multicellular preparation [8].

Biological context of enoxolone

• We conclude that the inhibitory effect of 18beta-glycyrrhetinic acid on GJIC in cardiomyocytes involves Src-mediated tyrosine phosphorylation of Cx43 [9].
• Treatment of a gap junctional intercellular communication (GJIC) inhibitor, 18beta-glycyrrhetinic acid, indicates that cell aggregation without GJIC does not perform the liver-specific functions for long periods [10].
• Inhibitory effect of 18beta-glycyrrhetinic acid on 12-O-tetradecanoyl phorbol-13-acetate-induced cutaneous oxidative stress and tumor promotion in mice [11].
• Among the absorption enhancers, 18beta-glycyrrhetinic acid and taurine decreased TEER and increased the permeability of heparin disaccharide in a dose-dependent and time-dependent manner with little or negligible cytotoxicity [12].

Anatomical context of enoxolone

• Effect of 18beta-glycyrrhetinic acid on electromechanical coupling in the guinea-pig renal pelvis and ureter [13].
• Induction of inducible nitric oxide synthase expression by 18beta-glycyrrhetinic acid in macrophages [14].
• Interestingly, 18beta-glycyrrhetinic acid stimulated a two- to three-fold increase in steroid production in these adrenal cells lacking intact cell junctions [15].
• Treatment with 18beta-glycyrrhetinic acid, a gap junction inhibitor, reduced the immunoreactivity of these proteins in a time- and dose-dependent manner, and caused the gap junction and adherens junction to separate longitudinally from the cell-cell contact sites, indicating the structural interdependency of these two junctions [15].
• The responses occur in both smooth muscle and endothelial cells, neither of which was blocked by 18beta-glycyrrhetinic acid [16].

Associations of enoxolone with other chemical compounds

• 4. In smooth muscle cells, ACh failed to induce a membrane current after gap junctions had been blocked with 18beta-glycyrrhetinic acid [17].
• 1 Heptanol, 18alpha-glycyrrhetinic acid (18alphaGA) and 18beta-glycyrrhetinic acid (18betaGA) are known blockers of gap junctions, and are often used in vascular studies [18].
• We have tested the effect of the gap junction inhibitor, 18beta-glycyrrhetinic acid (18betaGA) on electromechanical coupling in the guinea-pig renal pelvis and ureter by the sucrose gap technique [13].
• The effect of 18beta-glycyrrhetinic acid (GA), an agent which interferes with gap junction conductivity, on endothelium-dependent relaxation produced by substance P was investigated in isolated aortic rings of the guinea-pig [19].
• Expression of CAM proteins was examined in human umbilical vein endothelial cells (HUVEC) treated with a licorice component (isoliquiritigenin, 18beta-glycyrrhetinic acid, glycyrrhizin, formononetin, or ononin) and exposed to TNF-alpha [20].

Gene context of enoxolone

• Treatment with the gap junction blocker 18beta-glycyrrhetinic acid did not affect expression of MAGI-1 and JAM-1 in Cx32 transfectants [21].
• In contrast, other components recognized in licorice, 18beta-glycyrrhetinic acid, glycyrrhizin, formononetin, and ononin did not down-regulate the expression of VCAM-1 and/or PECAM-1 activated by TNF-alpha, implying that these components are inactive in modulating adhesion of leukocytes to stimulated endothelial cells [20].
• The results indicate that the combination of enoxolone glycoside withdrawal and IFN-alpha treatment reduces HBV replication more effectively than does interferon alone [22].
• Experiments with 18beta-glycyrrhetinic acid, a potent inhibitor of 11beta-HSD1, also indicated a minor or no role for 11beta-HSD1 [23].
• Pharmacological analyses indicated that the steroidogenic effect of 18beta-glycyrrhetinic acid was partially mediated by extracellular signal-related kinase and calcium/calmodulin-dependent kinase, a pathway distinct from the protein kinase A signaling pathway already known to mediate steroidogenesis in adrenal cells [15].

Analytical, diagnostic and therapeutic context of enoxolone

• Immunoprecipitation using anti-Cx43 and anti-p-Src antibodies showed that 18beta-glycyrrhetinic acid increased the association between p-Src and Cx43 and induced tyrosine phosphorylation of Cx43 [9].
• An unexpected case of primary pulmonary hypertension of the neonate (PPHN). Potential role of topical administration of enoxolone [24].
• A new method is described for the solid-phase extraction of 18beta-glycyrrhetinic acid from plasma or serum, with subsequent analysis by HPLC [25].
• Solid-phase extraction of 18beta-glycyrrhetinic acid from plasma and subsequent analysis by high-performance liquid chromatography [25].

References