The reform of medical system in China is accelerating the transformation process of the pharmaceutical department of medical institutions from the pharmaceutical supply and preparation to the clinical pharmaceutical care. “Promoting clinical rational use of drugs,ensuring the safety of clinical medication” is the core value of clinical pharmaceutical care. The pharmacovigilance is concerned with the detection,assessment,understanding and prevention of drug related problems,which reflects the diversity of the risk sources of clinical medication. The implementation of pharmacovigilance constitutes the cornerstone of pharmaceutical care in clinical practice.
To study the pharmacokinetic characteristics of roflumilast tablets in healthy Beagle dogs and compare relative bioavailability of the test and the reference formulations.Methods
Single dose of 500 μg test or reference preparations of roflumilast tablets were orally administered to 6 healthy male Beagle dogs in a randomized,cross-over study.Plasma concentrations were determined by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method.The pharmacokinetic parameters were calculated by DAS software and the relative bioavailability was compared.Results
The main pharmacokinetic parameters of the test and reference roflumilast tablets were as follows:the area under the concentration-time curve (AUC0-t) values were(16.33±9.79) and (16.21±10.43) μg·h·L-1,respectively; AUC0-∞values were(17.11±10.39) and (16.86±10.70) μg·h·L-1,respectively; the peak concentration (Cmax) values were(5.07±2.74) and (5.39±3.67) μg·L-1,respectively; the times to peak concerntration (tmax) were(1.04±0.51) and (0.96±0.56) h,respectively; the half-life (t1/2) values were(1.97±0.65) and (2.21±0.72) h,respectively.The relative bioavailability of the test tablets was (100.9±6.3)% compared with the reference tablets.Conclusion
The established HPLC-MS/MS method is suitable for the pharmacokinetic study of the roflumilast tablets,and the pharmacokinetic characteristics are similar between the test formulation and the reference one.
To investigate the effects of leflunomide on the proliferation and apoptosis of the lipopolysaccharide(LPS)-induced rat mesangial cells.Methods
The cultured rat glomerular mesangial cells were divided into the normal control group,the LPS group (final at 1 μg·mL-1),the A771726 group (final at 50 μg·mL-1) and the lipopolysaccharide+A771726 group (pretreated with 1 μg·mL-1 of LPS for 2 h,then added 50 μg·mL-1 of A771726).After 48 h's treatment,cell proliferation was measured by cell counting kit-8(CCK-8) assay,cell cycle and cell apoptosis were measured by flow cytometry.Results
Compared with the normal control group,LPS group significantly promoted the proliferation of rat glomerular mesangial cells(P<0.01),elevated the percentage of cells in G1 phase,and declined those in S and G2 phase (P<0.01).The apoptosis index of the rat glomerular mesangial cells significantly decreased in the LPS group[(0.244±0.079)%] compared with the normal control group[(2.098±0.380)% ](P<0.01).A771726 significantly inhibited the proliferation of rat glomerular mesangial cells(P<0.01),increased the percentage of cells in G1 phase and decreased those in S phase(P<0.01),and markedly increased the apoptosis index of rat glomerular mesangial cells[(9.564±0.539)%,P<0.01].Compared with the LPS group,LPS+A771726 obviously inhibited the proliferation of rat glomerular mesangial cells (P<0.01),raised the percentage of cells in G1 phase,decreased those in S phase(P<0.01),and increased the cell apoptosis index[(6.010±0.282)%,P<0.01].Conclusion
Leflunomide can inhibit the proliferation of the rat glomerular mesangial cells induced by LPS and lead to the cell apoptosis.
To investigate the effect of parecoxib sodium on postoperative cognitive dysfunction (POCD) in elderly depression rats.Methods
The total of 36 elderly male Sprague Dawley (SD) rats were divided into 3 groups:normal control group (n=6); surgical group (Sur group,n=15); paricoxib sodium group (Pare group,n=15).Depression models were established in rats except those in the normal control group.The 5 mg·kg-1 parecoxib sodium was i.p.injected in the Pare group 1 h prior to,8 h,2 d and 3 d post operation,respectively.And 0.9% sodium chloride injection was i.p.injected into the Sur group.Behavior and cognition of all animals were evaluated by open-field,sucrose consumption and Morris water maze tests.IL-6 and IL-1β expression were detected by Elisa.Results
The escape latency was (39.98±8.93) s in Pare group vs (47.15±10.87) s in Sur group (P<0.05); and the space exploration was (24.17±8.52) s vs (20.96±9.58) s (P<0.05).IL-6 expression was (72.86±6.82) in Pare group vs (79.26±4.19) ng·L-1 in Sur group,IL-1β expression was (350.73±28.04) vs (423.35±26.81) ng·L-1(P<0.05).The horizontal and vertical scores were significantly higher in Pare group than those in the Sur group(P<0.05).The sucrose consumption and sucrose preference were higher and the water consumption was lower in Pare group than those in the Sur group(P<0.05).Conclusion
Parecoxib sodium may improve postoperative cognition of elderly rats with depression,which being associated with decrease of IL-6 and IL-1β expression in hippocampus.
To investigate the effect of carvacrol on hippocampal injury,neurocyte apoptosis and endoplasmic reticulum stress related molecules like GRP78,caspase12,and CHOP in epileptic rats.Methods
The total of 80 male SD rats were randomly divided into normal control,model control,carvacrol at low dose(30 mg·kg-1) and high dose(60 mg·kg-1) groups,20 rats in each group.The consistent epilepticus model was established by treating lithium chloride-pilocarpine in rats.The neuronal injury and apoptosis were detected by Nissl staining and TUNEL staining,respectively.The levels of GRP78,caspase12 and CHOP were measured by Western blot analysis.Results
The nerve cell apoptosis index of the normal controls,model controls,carvacrol at low dose and that at high dose were (5.08±3.00),(34.43±0.55),(15.28±3.97),(10.62±2.56),respectively.Compared with the model control,carvacrol pretreatment significantly attenuated the hippocampal injury,increased the expression of GRP78 and decreased the expression of caspase12 and CHOP,especially for carvacrol at high dose.Conclusion
Carvacrol plays a role in hippocampus injury protection,which is in a dose-dependent manner and involved inpromoting GRP78 against hippocampal injury,mitigating caspase12 and CHOP induced ER apoptosis in epileptic rat.
To study the effects and mechanism of the xanthones from pericarps of mangosteen on human nasopharyngeal carcinoma cell line CNE2.Methods
Human nasopharyngeal carcinoma CNE2 cells were randomly divided into negative control group and different concentration of the xanthones from pericarps of mangostees. The negative control was normally cultured without drugs; The xanthones from pericarps of mangosteen groups were respectively treated by 200,400,600,800 μmol·L-1 xanthones 24,48,72 hours. MTT assay,Annexin -V/ PI double staining,and PI single staining were employed to investigate the action of the xanthones from pericarps of mangosteen on the cell cycle and apoptosis of CNE2 cells.And Caspase-3 kit was applied to investigate the activity of Caspase-3.Results
The xanthones from pericarps of mangosteen significantly inhibited the proliferation activity of human nasopharyngeal carcinoma cell line CNE2 in a dose-dependent manner,especially for which at 371.536 7 μmol·
The xanthones from pericarps of mangosteen remarkablly suppress proliferation of human nasopharyngeal carcinoma cell line CNE2 and promote their apoptosis,which may be involved in inhibition cells entering the S-phase and activating Caspase-3.
To study the effect of intermittent hypoxia and chronic hypoxia on rat blood pressure,and investigate the impact of gingko biloba extracts(GBE) on obstructive sleep apnea syndrome(OSAS) with hypertension in rats.Methods
Fifty healthy male Sprague-Dawley(SD) rats were randomly divided into 5 groups(n=10):normal control (NC),intermittent hypoxia(IH)model control,intermittent hypoxia with GBE administration,chronic hypoxia,and chronic hypoxia with GBE administration groups.The blood pressure was observed before and after experiment.The pathological changes of myocardia,renal artery and abdominal artery were observed by hematoxylin(HE) staining.The content of MDA,4-HNE and HIF-1α in serum were determined.The protein and mRNA expression of TLR4 and JNK in rat adipose tissue were detected.Results
Blood pressure of IH group was significantly higher than that in NC group and hypoxia group (bothintermittent and chronic,P<0.01).Compared with NC group,the myocardial cells swelled significantly and kidney tubules presented hydropic degeneration in both IH group and chronic hypoxia group.In intermittent hypoxia with GBE and chronic hypoxia with GBE groups,the myocardial cell and kidney tubules were without swelling and the abdominal artery was pathologicallyun changed compared with those in IH and chronic hypixia group.Compared with NC group,the level of MDA,4-HNE,HIF-1α in serum were remarkably higher in the IH group and chronic hypoxia group (P<0.05),the level of TLR4,JNK protein and the mRNA expression were obviously increased in adipose tissue of the IH and chronic hypoxia groups(P<0.01).However,the results of them in intermittent hypoxia with GBE intragastric administration group,chronic hypoxia with GBE intragastric administration group were lower compared with IH and chronic hypoxia group (P<0.05).Compared with NC group,those in the intermittent hypoxia with GBE intragastric administration group and chronic hypoxia with GBE intragastric administration group were lower than those in the IH and chronic hypoxia group (P<0.01).Conclusion
Intermittent hypoxia can elevate the blood pressure.GBE suppresses the protein and mRNA expression of TLR4,JNK in adipose tissue of OSAS and chronic hypoxia rats,and reduces the level of MDA,4-HNE,HIF-1α in serum,leading to less injury to organs and tissues by hypoxia.
To explore the effect and mechanism of curcumin on transient receptor potential channel 6(TRPC6) expression in cortical neuron of newborn rats with hypoxic-ischemic encephalopathy(HIE).Methods
Newborn SD rats (n=60) were randomly divided into three groups:sham-operated,model control,curcumin treatment groups (n=20) .Curcumin treatement group was intraperitoneal injected with 5,15,30,45,60 μmol·L-1 curcumin,and observed at 6,12,24,48,72 h,respectively.Cell viability was detected by MTT assay.The level of TRPC6 mRNA was detected by RT-PCR.The protein expression of TRPC6 and phosphorylation of p38 MAPK were detected by western blot.Results
Curcumin at 30 μmol·L-1 increased cell viability into(88.0±5.6)% (P<0.01) after treatment for 48 hours compared with the model control as(52.0±5.2)%.The expression levels of TRPC6 mRNA and protein were significantly increased after treatment with 30 μmol·L-1 of curcumin,the ratio of TRPC6 mRNA /GAPDH was 1.05±0.05 (P<0.05),and that of TRPC6/β-Tubulin was 0.93±0.04 (P<0.01).In addition,curcumin increased the phosphorylation of p38MAPK,with the ratio of pp38MAPK/p38MAPK was 0.65±0.04 (P<0.05).Conclusion
These results demonstrated that curcumin can obviously protect cortical neuron of HIE through TRPC6-p38MAPK pathway,and provide a novel insight into the manner in which curcumin participates in neuritogenesis.
To study the effect and mechanismof berberine combined with praziquantel on the liver fibrosis of Schistosoma japonicum infected rats.Methods
Eighty rats infected with Schistosoma japonicum were randomly divided into four groups(n=20).The model control group was untreated.The rats in praziquantel group were treated with praziquantel 500 mg·kg-1·d-1 by intragastric administration for 2 days,those in the berberine group were i.g.treated with berberine 150 mg·kg-1·d-1 for six weeks.The rats in berberine combined with praziquantel group were treated with berberine 150 mg·kg-1·d-1 for six weeks following praziquantel 500 mg·kg-1·d-1 i.g. for 2 days.By the 6th week after administration,the content of MDA,the activity of GSH-Px and the expressions of MMP-13,TIMP-1,typeⅠ and type Ⅲ collagen in liver tissue of mice were detected.Results
Compared with the model control group,the content of MDA and the expressions of TIMP-1,typeⅠ and type Ⅲ collagen in liver tissue were decreased obviously (P<0.05) and the activity of GSH-Px,the expression of MMP-13 and the ratio of MMP-13/TIMP-1 were increased obviously (P<0.05) in both praziquantel and berberine groups,but there was no significant difference between these 2 groups (P>0.05).The content of MDA(2.215±1.316 nmol·mg-1),TIMP-1 expressions (0.642±0.052),and typeⅠ (0.273±0.102) type Ⅲ (0.203±0.104) collagenin liver tissue were decreased obviously (P<0.05).GSH-Px(21.89±1.54) nU·mg-1,MMP-13 (0.588±0.027)and the ratio of MMP-13/TIMP-1 (0.726±0.138) were increased markedly (P<0.05) in the combination group compared with the monotherapy.Conclusion
Berberine may inhibit hepatic fibrosis by Schistosoma japonicum infection via reducing the level of oxidative stress and imbalance of expression ratio of MMP-13/TIMP-1,which may play a synergistic effect with praziquantel.
To study the expression of stromal cell-derived factor-1(SDF-1) on cerebral ischemia-reperfusion injury in rats and the effect of Tongqiao Huoxue decoction.Methods
A total of 30 male SD rats were randomly divided into groups a sham operation,a model control and Tongqiao Huoxue decoction at three different doses,6 rats in each group.The model of middle cerebral artery occlusion was set up in rats,the experimental group was perfused with Tongqiao Huoxue decoction,the sham operation and model control groups were treated with distilled water.The changes of SDF-1 were detected on 3,7,14 d after ischemia-reperfusion injury by enzyme-linked immunosorbent assay (ELISA).Results
SDF-1 in the model control group was expressed at different time point,which enhanced from the third day(545.92±21.81) pg·mL-1,and reached the peak on the 7th day (574.82±26.58) pg·mL-1; SDF-1 started to decline on the 14th days (558.97±24.17) pg·mL-1,which were higher than the sham operation group[(350.09±9.36),( 356.62±10.86),( 356.62±9.64) pg·mL-1].The content of SDF-1 in the middle-dose and high-dose Tongqiao Huoxue decotion group was (560.84±32.37),(655.95±14.87),(625.18±14.77) pg·mL-1and (595.07±19.19),(760.39±46.90),(679.26±37.01) pg·mL-1,respectively,which were higher than the model control group.Conclusion
SDF-1 increases significantly after ischemia-reperfusion injury,and Tongqiao Huoxue decoction could promote the increase.
To investigate the influence of Yangxin Fumai potion on liver microsomal CYP1A2,2E1 and 3A4 in rats.Methods
Twenty-four SD rats were divided into 4 groups at random(n=6):the experimental groups were given with Yangxin Fumai potion at 2.50,5.00 and 10.00 mL·kg-1,respectively,by gastric gavage for 14 days,while the normal control group was given with 0.9% sodium chloride injection at 5.00 mL·kg-1.Upon differential centrifugation of liver microsomals,the metabolic rates of CYP 1A2,2E1 and 3A4 probe drugs were detected by HPLC.Results
No significant difference was presented in the Yangxin Fumai potion at low and medium doses,which compared with those in the normal control group (P>0.05)in vitro.The activities of CYP1A2,CYP2E1 and CYP3A4 in the high dosage of Yangxin Fumai potion group were(28.43±4.49)%,(42.23±1.44)%,(11.20±0.98)%,respectively,which were higher than those in the normal control group(15.51±4.26)%,(31.54±3.37)%,(5.66±0.65)%,respectively (P<0.05).Conclusion
Yangxin Fumai potion can activate liver microsomal CYP 1A2,2E1 and 3A4 of rats.