The Effect of Glycyrrhetinic Acid on Pharmacokinetics of Cortisone and Its Metabolite Cortisol in Rats

Abstract

The purpose of this paper is to study pharmacokinetics of cortisone (E) and its metabolite cortisol (F) in rats after administration of glycyrrhetinic acid (GA) and cortisone. Healthy male SD rats were randomized to be given 20 mg/kg E or E combined with 10 mg/kg GA. Blood samples were collected at 5, 10, 20, 40, 60, 90, 120, 150, 180, and 240 min after administration. The serum concentrations of E and F were determined by HLPC and pharmacokinetic parameters were calculated using DASver2.0 software. The parameters of AUC(0−t), AUC(0−∞), and Cmax for E in the group of E + GA were significantly higher than those in the group of E (P < 0.01); the half-time (t1/2β) was extended compared to E (P < 0.05) and CL/F was dropped obviously (P < 0.01). The rise in AUC(0−t), AUC(0−∞), and Cmax for cortisol in the group of E + GA was significantly compared to the group of E (P < 0.01). CL/F was lower than E (P < 0.01) and the half-time (t1/2β) was slightly extended. In this study, we find that GA restrains the metabolism of E and F and thus increases AUC, t1/2β, and Cmax of E and F, which may be related to its inhibition effect on 11β-hydroxysteroid dehydrogenase (11β-HSD).

Effect of the liquorice root derivatives on salt and water balance in a teleost fish, rainbow trout (Oncorhynchus mykiss)

“…The actions of LRDs on 11β-HSD2 thereby lead to an increase in cortisol availability in mineralocorticoid target tissues (Armanini et al, 2004). As a consequence, although LR is a broadly acknowledged botanical with many medicinal benefits, the harmful consequences of excess consumption of LR or LRDs manifest as pseudohyperaldosteronism that can cause hypertension as well as salt and water imbalance (Ruszymah et al, 1995;Armanini et al, 2004;Ferrari, 2010;Al-Dujaili et al, 2011;Lin et al, 2012).…”

The Host-Protective Effect of Arabinosylated Lipoarabinomannan against Leishmania donovani Infection Is Associated with Restoration of IFN-γ Responsiveness

“…Leishmania deactivates the macrophage functions facilitating the parasite infection and propagation within the cell [ 7 , 47 ]. A key immunomodulatory activity required for eliminating Leishmania is IL-12-dependent production of IFN-γ by Th1 cells [ 14 , 15 ], IFN-γ activates macrophages by iNOS-dependent elimination of the parasite Leishmania [ 16 ].…”

“…For example, L . donovani lowers IFN-γ responsiveness in macrophages [ 7 , 48 ] by lowering IFN-γ receptor expression and by enhancing phosphatase-mediated STAT-1 inactivation [ 31 , 32 , 34 ]. Corroborating to these observations, IFN-γ-deficient mice were more susceptible to Leishmania infection than the wild-type controls [ 49 ].…”

“…In addition, emergence of drug-resistant parasites [ 5 ] compels development of an immunotherapeutic principle. As Leishmania expressed lipophosphoglycan (LPG) interacts with the macrophage expressed TLR2 [ 6 , 7 ], which subsequently regulates the expression and function of the leishmanial DNA recognizing TLR9 [ 8 , 9 ], TLR2 is targeted for developing an anti-leishmanial immunotherapy.…”

Invitro and Invivo Inhibition of Metyraponemetabolism by Glycyrrhetinic Acid in Male Wistar Rats

“…Therefore, it is not clear whether the inhibitor affects the pharmacokinetics of MP and its metabolites. Of the known 11β-HSD1 inhibiters [15,16], we focused our attention on glycyrrhetinic acid (GA) and examined its effect on the metabolism of MP in the rat liver and testis invitro and the pharmacokinetics invivo.…”