Screening for potential bioactive components of Yin-zhi-huang using high bilirubin HepaRG cells incubating with serum from animals / 药学学报

A hyper-bilirubin cell model was established for its relevance to the pathological state of jaundice in human. This model was used to screen for the pharmacological components of Yin-Zhi-huang (YZH). Total bilirubin, indirect bilirubin in cells, and direct bilirubin in extracellular fluid were quantified after HepaRG cells were incubated with serum from rats injected with multiple components of YZH. Cellular uptake was determined by dynamic multiple reaction monitoring (DMRM) using LC-MS/MS. We found that the stable hyper-bilirubin HepaRG cell model could be established by incubating cells with 40 μg·mL-1 bilirubin and 50 μg·mL-1 probenecid. When the hyper-bilirubin cell model was incubated with serum from rats of YZH injection, there were 52.4% and 60.1% decrease in intercellular total bilirubin and indirect bilirubin, respectively, and 52.5% increase in extracellular direct bilirubin. Using DMRM mode, 53 components could be determined, and 8 potential bioactive candidates were identified from the serum. This method could be used to screen for bioactive metabolites of YZH. This strategy is simple, highly active, sensitive and specific, providing a new method for high throughput screening of therapeutic or toxic metabolites from traditional Chinese medicine. The regulations of Ethics Committee in the First Hospital of Lanzhou University were abided in the rat experiment of this study.

Effects of metoprolol or/and pravastatin on the pharmacokinetics of metformin in rats / 药学学报

This study investigates the effects of metoprolol (METO) or/and pravastatin (PRAV) on the pharmacokinetics of metformin (METF) in rats. Twenty-eight male SD rats were divided into METF group, METF+METO group, METF+PRAV group and METF+METO+PRAV group. Blood samples were collected at 10, 20, 40, 60, 90, 120, 180, 240, 360, 480 and 600 min after oral administration of metformin, and concentration of metformin in plasma was determined by HPLC. Compared to the METF group, Cmax of metformin was significantly decreased (P0-t, t1/2 and V were significantly increased in the METF+METO group; t1/2 was significantly decreased in the METF+PRAV group; Cmax was significantly decreased and MRT0-t was significantly increased in the METF+METO+PRAV group. Compared to the METF+METO group, MRT0-t of metformin was significantly decreased in the METF+METO+PRAV group. Compared to the METF+PRAV group, Cmax of metformin was significantly decreased (P0-t, t1/2 and V were significantly increased in the METF+METO+PRAV group. There exist multiple drug interactions of metformin, metoprolol and pravastatin in rats.

Study of pharmacokinetics of digoxin in ovariectomized rats model / 药学学报

This study aims to investigate the change of plasma concentration of digoxin (DIG) in rats with ovariectomy. Twelve female SD rats were randomly assigned into ovariectomized group and sham group (n = 6). All rats plasma was collected after a single dose of 2 mg x kg(-1) DIG administrated orally, serum DIG concentration was determined by LC-MS/MS. The level of P-gp in the intestinal was analyzed by Western blotting. Pharmacokinetic calculations were performed on each individual using DAS 2.0 practical pharmacokinetic software. Compared with the sham group, C(max) of ovariectomized group decreased significantly (P < 0.01). There was no significant difference of AUC(0-t), and the level of P-gp was elevated in ovariectomized group. It was found that C(max) of DIG was significantly reduced after ovariectomy, and the change was associated with the decreased level of estrogen, which contributes to the increased level of P-gp.

Simultaneous determination of repaglinide and pravastatin sodium in rat plasma by LC-ms/MS and its application on pharmacokinetic interactions study / 药学学报

The study aims to establish a method for simultaneous determination of repaglinide and pravastatin sodium in rat plasma by LC-MS/MS and to study its pharmacokinetic interactions. Eighteen male SD rats were divided into repaglinide group, pravastatin sodium group and co-administration group. Blood samples were collected at different times after oral administration. Repaglinide and pravastatin sodium in rat plasma were separated by Agilent HC-C18 with the mobile phase consisting of methanol-0.1% formic acid (80 : 20). Detection and quantification were performed by using ESI-MS. The detector was operated in selected Reaction-monitoring mode at m/z 453.3-->230.1 for repaglinide, m/z 447.2-->327.4 for pravastatin sodium and m/z 285.1-->192.9 for diazepam as the internal standard. The calibration curve obtained was linear (R2>0.99) over the concentration range of 9.77-10,000 ng.mL-1 for repaglinide and 4.88-625 ng.mL-1 for pravastatin sodium. Compared with the single administration group, Cmax and AUC0-6h of repaglinide increased significantly (P<0.05) and tmax of pravastatin sodium prolonged (P<0.05) in co-administration group. The method is found to be simple, sensitive and accurate for determining the concentration of repaglinide and pravastatin sodium in rat plasma. There exists pharmacokinetic interactions in the co-administration of repaglinide and pravastatin sodium.

Secretion and action of insulin among Han and Uygur subjects with impaired fasting glucose and impaired glucose tolerance,from Xinjiang / 中华流行病学杂志

Objective To compare insulin secretion and action with impaired fasting glucosc (IFG),impaircd glucose tolerance (IGT) and combined glucose intolerance (CGI,IFG and IGT) between Han and Uygur populations living in Xinjiang.Methods A multicenter cross-section survey (The Third Diabetes Epidemiological Survey in China) was conductcd in Xinjiang from 2007 to 2008 including 2203 subjects (Han 1118,Uygur 1085) underwent an oral glucosc test (OGTT).Homeostasis model assessment on insulin resistance (HOMA-IR) and β cell function (HOMA-β)were calculated.The ratio of incrcmcntal insulin(Δ130 ) and glucose (ΔG30)response was used to evaluate the early insulin secretion.ΔI30/ΔG30/HOMA-IR was used to evaluate the glucosc disposition index (DI).Results There were differences noticed regarding the waist circumstances (WC),body mass index (BMI),lipids,0 and 120 min insulin lcvcls in different glucose tolerance status between the Hans and Uygurs.Data related to NGT,IFG,CGI,WC from the Uygurs was significantly diffcrcnt from that of the Hans (P＜0.01),while the NGT,IFG,IGT and 120-minute plasna insulin levels of the Hans were significantly different from that of the Uygurs (P＜0.01).HOMA-IR and HOMA-β in Hans were significantly different from those of the Uygurs (P＜0.01).There were significant differences noticed on data reoated to Δ130/ΔG30,and DI among the two populations with different ethnicities.Conclusion Regarding the regulation of impaired glucose,the insulin resistance among the Hans was significantly different from that of the Uygurs,while there seemed to be a compensatory secretion of pancreatic β cells which played the role of maintaining blood glucose homeostasis.

Improvement in blood glucose fluctuations of insulin-treated type 1 diabetic patients with additional use of acarbose and assessed by continuous blood glucose monitoring program / 中华流行病学杂志

Objective To investigate the effect of combined use of insulin and acarbose on glucose excursion in type 1 diabetic patients.Methods 120 cases were randomly divided into control group and observation group.The control group received preprandial ultra-short effect insulin and long-acting insulin before bedtime while the observation group received acarbose 50 mg added to the medicine taken by the control group.Continuous Glucose Monitoring System (CGMS) was used to watch the blood glucose fluctuations.Data related to blood glucose level,glucose excursions after meals and hypoglycemia at night were compared between patients in the two groups.Results The average blood glucose (9.37 ± 1.70) mmol/L,the largest amplitude of glycemic excursions (LAGE) ( 11.42 ± 2.73 ) mmol/L,hyperglycemia-area under curve 0.89 ± 0.54,mean amplitude of glycemic excursions (MAGE) (5.13 ± 2.23) mmol/L,M-value (18.93 ± 11.43) mmol/L and insulin dosage (42.11 ± 14.42)U/day of observation group were significantly lower than in the control group (P＜0.05 ).Glucose excursions after meals and the times( 0.33 ± 0.50 )/day,the maintenance time (43.75 ± 43.50)/min and low glycemic index ( LBGI ) (0.005 ± 0.002 ) mmol/L of hypoglycemia at night were also significantly lower than in the control group,with statistically significant (P＜0.05) differences.Conclusion The blood glucose fluctuation was significantly improved,with the decrease of insulin dosage while both glucose excursions and hypoglycemia at night reduced in patients with typel diabetes mellitus after the acarbose treatment.We suggested that this program deserve further observation.