Context: Asiatic acid has been reported to possess a wide range of pharmacological activities.Objective: This study investigates the effects of glycyrrhizin on the pharmacokinetics of asiatic acid in rats and its potential mechanism.Materials and methods: The pharmacokinetics of orally administered asiatic acid (20 mg/kg) with or without glycyrrhizin pretreatment (100 mg/kg/day for seven days) were investigated using a LC–MS method. Additionally, the Caco-2 cell transwell model and rat liver microsome incubation systems were used to investigate the potential mechanism of glycyrrhizin’s effects on the pharmacokinetics of asiatic acid.Results: The results showed that the Cmax (221.33 ± 21.06 vs. 324.67 ± 28.64 ng/mL), AUC0–inf (496.12 ± 109.31 vs. 749.15 ± 163.95 μg·h/L) and the t1/2 (1.21 ± 0.27 vs. 2.04 ± 0.32 h) of asiatic acid decreased significantly (p < 0.05) with the pretreatment of glycyrrhizin. The oral clearance of asiatic acid increased significantly from 27.59 ± 5.34 to 41.57 ± 9.19 L/h/kg (p < 0.05). The Caco-2 cell transwell experiments indicated that glycyrrhizin could increase the efflux ratio of asiatic acid from 1.63 to 2.74, and the rat liver microsome incubation experiments showed that glycyrrhizin could increase the intrinsic clearance rate of asiatic acid from 138.32 ± 11.20 to 221.76 ± 16.85 μL/min/mg protein.Discussion and conclusions: In conclusion, these results indicated that glycyrrhizin could decrease the system exposure of asiatic acid, possibly by inducing the activity of P-gp or CYP450 enzyme.
The structural and dielectric properties of Na0.5Bi0.5TiO3 (NBT) ceramics and crystals have been investigated and are compared to that of Pb(Zr0.55Ti0.45)O3 (PZT55/45) and Pb(Mg1/3Nb2/3)0.72Ti0.28O3 (PMNT 72/28) ceramics. X‐ray diffraction (XRD) profiles for (100), (110), (111), (200), (220), and (222) (referred to cubic structure) reveal that the monoclinic structure with Cc space group exists both in the NBT single crystal and ceramics. The diffraction profile obtained with high resolution laboratory XRD for the NBT single crystal can be well described, using Cc model instead of R3c model. The dielectric constant of NBT below Thump shows some similarity to that of PZT45/55 ceramics below 50°C in which oxygen octahedron rotations cause the frequency dispersion of the dielectric constant. The temperature‐dependent dielectric constant for NBT can be deconvolved into two independent processes. The lower temperature process shows a typical relaxor characteristic and follows the Vogel‐Fulcher relationship. The other process at higher temperature shows less frequency‐dependent behavior. Comparing the dielectric constant of NBT with that of PZT55/45 and PMNT72/28 reveals that both oxygen octahedral rotations and random electric fields play an important role in the frequency dispersion of the dielectric constant for NBT relaxor feroelectric.
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