ABSTRACT
Aim To investigate the inhibitory effects of the novel compounds YZG-330 and YZG-331 in central nervous system. Methods The sedative effect was investigated by recording the spontaneous locomotor ac-tivity in mice. The hypnotic effect was evaluated by the latency and duration of the loss of righting reflex ( LORR) in the threshold dosage of sodium pentobarbi-tal treated mice. The two compounds induced the mice that had woken up after a threshold dosage pentobarbi-tal sodium to fall asleep again. The levels of GABA and Glu in brain were measured by HPLC-ECD. Re-sults The results showed that spontaneous locomotor activities decreased in YZG-330 (0.125, 0.5,2 mg·kg-1 ) treated mice and YZG-331 (1.25, 5, 20 mg· kg-1 ) treated mice. YZGs could extend the duration of the loss of righting reflex in threshold dosage of sodium pentobarbital treated mice, and significantly shorten sleep latency. YZGs were able to allow the mice that had woken up after a threshold dosage pentobarbital so-dium to fall asleep again. YZG-331 (40 mg·kg-1 ,i. g. ) could significantly increase GABA level in hypo-thalamus and cerebral cortex. The content of GABA had no significant change after YZG-330 ( 2 mg · kg-1 , ig. ) administration. Conclusions YZG-330 and YZG-331 have potent sedative and hypnotic effects. The efficacy of YZG-330 is stronger than that of YZG-331 , but the mechanism of two compounds sounds different.
ABSTRACT
OBJECTIVE: To confirm the structures of the impurities of cefatrizine propylene glycolate.
ABSTRACT
OBJECTIVE: The aim of our work was to study the effects of C-18 epimers of glycyrrhetinic acid, 18α-glycyrrhetinic acid (α-GA) and 18β-glycyrrhetinic acid (β-GA) on the function and expression of P-gp in Caco-2 cell monolayers. METHODS: Caco-2 cells were cultured, the effects of P-gp function were analyzed by means of rhodamine accumulation test, real-time PCR was used to measure the expression of MDR1 mRNA and western blot was used to analysis P-gp expression in Caco-2 cell. RESULTS: In the rhodamine accumulation test, middle and high concentrations (1 and 10 μmol · L-1) α-GA and high concentration (10 μmol · L-1) β-GA decreased the cellular rhodamine concentration. At high concentrations (10 μmol · L-1), α-GA up-regulated the expression of MDR1 mRNA while β-GA has no effect on the expression of MDR1 mRNA at three test concentrations. α-GA up-regulated the expression of P-gp protein at high concentrations (10 μmol · L-1) while β-GA has no effect on the expression of P-gp protein at three test concentrations. CONCLUSION: Our findings provide experimental evidence that α-GA up-regulated both function and expression of P-gp while β-GA only up-regulate the function of P-gp.
ABSTRACT
OBJECTIVE: To study the effects of C-18 epimers of glycyrrhetinic acid, 18α-glycyrrhetinic acid(α-GA) and 18β-glycyrrhetinic acid(β-GA), on membrane transport of P-gp substrate rhodamine 123 in Caco-2 cell monolayers. METHODS: MTT assay was applied to determine the maximum non-cytotoxic dose of α-GA, β-GA and verapamil to ensure the activity of the cells during the test and to consult the maximum test concentration of each drug; appropriate Caco-2 monolayers were established in Transwell™ plates. ELISA Reader was applied to detect the concentration of Rho-123 in transfer fluid. The bi-directional transport of Rho-123 after being treated by instantaneous action and incubation with α-GA and β-GA for 72 h was studied. RESULTS: High concentration (10 μmol · L-1) of α-GA induced the efflux of Rho-123 both in the instantaneous action test and the incubation test. High concentration (10 μmol · L-1) of β-GA induced the efflux of Rho-123 only in the incubation test. The transport from AP to BL was not affected by any test drugs. CONCLUSION: The results of the transport experiments of P-gp substrates in Caco-2 monolayers indicated that α-GA and β-GA can induce the efflux function of P-gp and accelerate the excretion of P-gp substrates. It may be one of the mechanisms of that glycyrrhizin preparation enhances liver detoxification. Copyright 2012 by the Chinese Pharmaceutical Association.