[Synergistic Effects of Clopidogrel and Xuesaitong Dispersible Tablet by Modulating Plasma Protein Binding].

Objective: The ginsenoside Rb1,which account for platelet aggregation of Xuesaitong dispersible tablet, was selected to investigate the synergistic effects of clopidogrel( CPG) and Xuesaitong dispersible tablet drug by modulating plasma protein binding rate aspect. Methods: The HPLC and equilibrium dialysis were employed to determine the concentration of Rb1 both in dialysate( PBS) and blank plasma from healthy volunteer blood donors. The differences in protein-binding rate between Xuesaitong dispersible tablet alone( the concentration of ginsenoside Rb1 were 5. 0,1. 0,0. 4 µg / m L,respectively) and combined with CPG( each add CPG 2 µg / m L) were then compared. The three-dimensional spatial structure of the blank plasma albumin( HSA) in the subjects was construct by rabbit plasma albumin( PDB ID 3V09) template and evaluated by PRO-CHECK and ERRAT methods. Molecular simulation technique was used to display the competition mechanism with human plasma protein. Results: The protein binding rate of Xuesaitong dispersible tablet alone group in plasma PBS and human plasma at high( the concentration of ginsenoside Rb1 were 5. 0 µg / m L),middle( the concentred of ginsenoside Rb1 were 1. 0 µg / m L) and low( the concentration of ginsenoside Rb1 were 0. 4 µg / m L) concentrations were( 58. 17 ±3. 82) %,( 57. 43 ± 3. 21) %,( 55. 63 ± 3. 42) % respectively. When combined with CPG( each add CPG 2 µg / m L),the protein binding rate value were decline to( 46. 54 ± 3. 35) %,( 49. 25 ± 3. 56) %,( 48. 15 ± 3. 76) %,respectively. The molecular simulation results suggested that the two compounds have competitive synergistic effects with human plasma protein. Conclusion: The present investigation suggestes that there are synergistic effects of CPG and Xuesaitong dispersible tablet by modulating plasma protein binding rate of ginsenoside Rb1.

[Computational Pharmacological Study on Clopidogrel Metabolism Enzymes Influenced by Fufang Danshen Dripping Pill].

OBJECTIVE: To investigate the effect of Fufang Danshen Dripping Pill on Clopidogrel metabolism enzymes target such as human liver carboxylesterasel (CES1), cytochrome P450 3A4, CYP450 2C19, CYP450 1A2, and CYP450 2B6, and to interpret the interaction effects. METHODS: The CES1, cytochrome P450 3A4, CYP450 2C19, CYP450 1A2 and CYP450 2B6 which involved in Clopidogrel metabolism were selected at first, the chemical ligand database were created then, and finally the interaction effects between the ligand database and Clopidogrel metabolism target were explored. RESULT: 1 MX1 (CES1), 3NXU (CYP450 3A4), 4GQS (CYP450 2C19), 2HI4 (CYP450 1A2) and 3IBD(CYP450 2B6) as well as THA, RIT, OXU, Chlorzoxazone and CPZ were used as receptors and cutoff for each target respectively. The number of hits with potentially positive activities with metabolism enzymes target from the bioactive compounds in the preparation was 29, 8, 31, 51 and 44, respectively. These computational pharmacological docking studies were in accordance with the referenced cocktail experiment results. CONCLUSION: It is suggested that Fufang Danshen Dripping Pill has inhibitory effects on Clopidogrel metabolism enzymes target such as CES1, Cytochrome P450 3A4, CYP450 2C19, CYP450 1A2 and CYP450 2B6.

[Effect of Cordyceps sinensis sporocarp on learning-memory in mice].

OBJECTIVE: To study the effect of extracts of Cordyceps sinensis sporocarp on learning-memory in scopolamine treated mice and the possible mechanism. METHODS: ICR mice were randomly divided into five groups: sham control, model, piracetam and CSE 0.5, 1 g/kg. Lotomotor activity was assessed. Morris water maze was used to evaluate the memory ability of mice 30 min later after ip scopolamine 1.0 mg/kg BW. Then acitivity of AchE was measured after behavioral test. RESULTS: CSE had no influence on lotomotor activity. However, CSE 0.5, 1 g/kg both shortened escape latency and increased times of come-crossing platform in Morris water maze, meanwhile activity of AchE in the brain was decreased by CSE. CONCLUSION: CSE can significantly improve the learning and memory impairment in mice induced by scopolamine, which may be correlated with the inhibition of activity of AchE.

Clinical effect and action mechanism of Weicao Capsule in treating gout.

OBJECTIVE: To study the therapeutic effect of Weicao Capsule (WCC) on gout. METHODS: Two hundred gout patients were assigned to two groups. The treated group was treated with WCC and the control group was treated with Tongfengding Capsule. Both groups were given the respective treatments orally 3 times a day, 2 capsules each time with 2 weeks as one course and all patients received 2 successive courses of treatment. Changes of blood beta(2)-microglobulin (beta(2)-M), hemoglobin (Hb), 24 h urinary protein (24 h UP), pH value of urine and blood uric acid (BUA) as well as kidney function were observed. RESULTS: After treatment, level of beta(2)-M got lowered significantly, Hb and 24 h UP, blood urea nitrogen, serum creatinine and the clearance rate of creatinine, as well as blood lipids all improved obviously in the treated group (all P<0.01), while these parameters remained unchanged in the control group (P>0.05). The pH value of urine was improved in both groups showing an insignificant difference between them (P>0.05). BUA was decreased in both groups with a decrease to a larger extent in the treated group (P<0.01). The total effective rate was 87% in the treated group, which was superior to that in the control group (62%, P<0.05). CONCLUSION: WCC has a favorable therapeutic effect on gout and its mechanism of action for improving renal function and reducing urinary protein could be related with the lowering of blood beta(2)-M, BUA and lipids.

[Randomized controlled trial on haiguiyuyang capsule in the treatment of duodenal ulcer].

OBJECTIVE: To assess the efficacy and safety of haiguiyuyang capsule in the treatment of duodenal ulcer (also diagnosed as weiwan pain and hanrecuoza syndrome according to the theory of TCM). METHODS: This is a multi-center clinical trial cooperatively conducted from May 2003 to March 2004 in accordance to the principle of informed consent, to the criteria for subject inclusion, exclusion, discontinuation, and to the relevant guidelines for evaluating the therapeutic effects of new TCM drugs. The design of double-blind, double-dummy and randomized controlled trial was adopted. 438 patients were randomized to the Test group (n = 330, treated with haiguiyuyang capsule) and to the Control group (n = 108, treated with ranitidine). The therapeutic course for both groups was 6 weeks. RESULTS: Regarding the efficacy in treating duodenal ulcer, in the Test group, the Marked Efficacy Rate was 66.37% and the Total Efficacy Rate was 82.13%; in the Control group, the Marked Efficacy Rate was 68.61% and the Total Efficacy Rate was 93.34%; there was no significant difference between the two groups (P>0.05). Regarding the efficacy in treating the syndrome diagnosed by TCM, in the Test group, the Marked Efficacy Rate was 70.31% and the Total Efficacy Rate was 93.34%; in the control group, the rates were 71.29% and 91.66% respectively; there was no significant difference between the two groups (P>0.05). Besides, regarding the abatement of distention and fullness of stomach after treatment, the haiguiyuyang capsule was better than ranitidine (P<0.05). No adverse side-effect was observed. CONCLUSION: The efficacy of haiguiyuyang capsule in treating duodenal ulcer is similar to that of ranitidine. No obvious adverse effect of it was observed in this trial.