Disease relevance of CCRIS 3963

• 18 Beta-glycyrrhetinic acid triggers curative Th1 response and nitric oxide up-regulation in experimental visceral leishmaniasis associated with the activation of NF-kappa B [1].
• The principal side effects of the drug carbenoxolone (Biogastrone; 18 beta-glycyrrhetinic acid sodium hemisuccinate) are sodium retention, hypokalemic alkalosis, suppressed plasma renin, and hypertension [2].
• Anti-inflammatory activity of the stereoisomers, 18 alpha and 18 beta-glycyrrhetinic acid (18 alpha and 18 beta-GA), obtained from Glycyrrhizae Radix, was investigated by using carrageenan-induced edema in mice and 18 alpha-GA was found to be more active than 18 beta-GA [3].

High impact information on CCRIS 3963

• We used 18alpha-glycyrrhetinic acid (alphaGA) to block gap junction conductance, which was assessed by fluorescence recovery after photobleaching [4].
• This response was significantly reduced by antisense to Cx43 and by the gap junction and hemichannel inhibitors 18 beta-glycyrrhetinic acid and carbenoxolone, even in cells without physical contact, suggesting the involvement of Cx43-hemichannels [5].
• In this study, we showed that the specific gap junction inhibitor 18 beta-glycyrrhetinic acid did not influence the inhibitory effect of Cx43 on Skp2 expression [6].
• Treatment with a GJIC blocker, 18 beta-glycyrrhetinic acid, resulted in decreases of occludin and claudin-1 at cell borders in the stable transfectants [7].
• Co-cultures were treated with the blocking agents carbenoxolone (CBX; 25 microM), 18alpha-glycyrrhetinic acid (AGA; 10 microM), vehicle or the inactive blocking analogue glycyrrhizic acid (GZA; 25 microM) [8].

Biological context of CCRIS 3963

• Kinetics and dynamics of orally administered 18 beta-glycyrrhetinic acid in humans [9].
• Both 1 mM ouabain (pD(2) = 5.90 +/- 0.07; R(max) = 50.4 +/- 6.5 %) and 100 microM 18alpha-glycyrrhetinic acid (pD(2) = 6.04 +/- 0.14; R(max) = 40.9 +/- 5.8 %) opposed anandamide-induced vasorelaxation [10].
• This H2O2-induced astrocyte cell death is not affected when gap junctions are inhibited by several uncoupling agents, including 18alpha-glycyrrhetinic acid, halothane, heptanol, and endothelin-1, indicating that the proportion of cell death is not related to the level of GJC [11].
• Both calcium wave propagation and Lucifer Yellow transfer were blocked by the gap junction inhibitor 18alpha-glycyrrhetinic acid [12].
• We found that beta-glycyrrhetinic acid is a potent inhibitor of the classical complement pathway (IC50 = 35 microM), whereas no inhibitory activity was observed towards the alternative pathway (IC50 > 2500 microM) [13].

Anatomical context of CCRIS 3963

• In this study, GJIC in normal 16 myoblasts was inhibited using the known blockers l-octanol and beta-glycyrrhetinic acid (beta-GA) [14].
• Preincubation of tissues with 18 alpha- or 18 beta-glycyrrhetinic acid, inhibitors of gap junction communication, increased the input resistance and depolarised the endothelial cells, and inhibited the hyperpolarising effect of levcromakalim [15].
• They were similarly attenuated by the gap junction inhibitors 18alpha-glycyrrhetinic acid (18alpha-GA) and Gap 27 peptide which interrupt direct endothelium-smooth muscle communication without themselves affecting smooth muscle tone [16].
• Its sensitivity to extracellular Ca2+ and gap junction channel blockers (18alpha-glycyrrhetinic acid, palmitoleic acid, heptanol), and its absence in non-transfected HeLa cells suggested that it is carried by Cx45 hemichannels [17].
• Inhibition of interleukin-8 production in the human colonic epithelial cell line HT-29 by 18 beta-glycyrrhetinic acid [18].

Associations of CCRIS 3963 with other chemical compounds

• A gap junction blocker, 18alpha-glycyrrhetinic acid, revealed enhanced contractions to U46619 in the absence or presence of l-NNA [19].
• 6 THC (10 and 100 microM) inhibited endothelium-derived relaxing factor (EDHF)-mediated responses to carbachol in a manner similar to the gap junction inhibitor 18alpha-glycyrrhetinic acid [20].
• Relaxations and elevations in cAMP evoked by ACh were abolished by 18alpha-glycyrrhetinic acid, which disrupts gap junction plaques, whereas the corresponding responses to A-23187 were unaffected by this agent [21].
• There was extensive calcein dye transfer in a cohort of Texas red dextran-labeled cells, but this was almost completely abolished by the gap junction inhibitor beta-glycyrrhetinic acid and the connexin43 mimetic peptide GAP 27 [22].
• The ACh-induced EDHF-type relaxation was significantly weaker in STZ-induced diabetic rats than in control rats, and in both groups of rats it was attenuated by 18alpha-glycyrrhetinic acid (18alpha-GA), an inhibitor of gap junctions, and enhanced by IBMX, a cAMP-phosphodiesterase (PDE) inhibitor [23].

Gene context of CCRIS 3963

• We investigated the role of 18 beta-glycyrrhetinic acid (GA), a saponin isolated from licorice roots, on TNF-alpha-induced IL-8 production in human colonic epithelial cells [18].
• Moreover, functional inhibition of the gap junction by 18alpha-glycyrrhetinic acid treatment or inhibition of Cx43 synthesis with oligodeoxyribonucleotide antisense decreased the effect of HUVEC cocultures on HBMSC differentiation [24].
• Gap junction inhibitor 18alpha-glycyrrhetinic acid partially inhibited, whereas inhibitors of cytochrome P450 did not affect the EDHF-mediated relaxations [25].
• A novel 18 beta-glycyrrhetinic acid analogue as a potent and selective inhibitor of 11 beta-hydroxysteroid dehydrogenase 2 [26].

Analytical, diagnostic and therapeutic context of CCRIS 3963

• Determination of 18 beta-glycyrrhetinic acid in biological fluids from humans and rats by solid-phase extraction and high-performance liquid chromatography [27].
• A high-performance liquid chromatographic (HPLC) method has been developed for measuring 18 beta-glycyrrhetinic acid (GRA) in human plasma in the range of 0.1-3 micrograms/ml [28].
• Gap junction uncoupler 18alpha-glycyrrhetinic acid (10(-4) mol/l) caused an uncontrollable increase in basal perfusion pressure making it impossible to test against acetylcholine-induced dilation [29].
• Determination of urinary 18 beta-glycyrrhetinic acid by gas chromatography and its clinical application in man [30].

References