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1.
Article in Chinese | WPRIM | ID: wpr-928064

ABSTRACT

This study explored the anticoagulant material basis and mechanism of Trichosanthis Semen and its shell and kernel based on spectrum-effect relationship-integrated molecular docking. High performance liquid chromatography(HPLC) fingerprints of Trichosanthis Semen and its shell and kernel were established. Prothrombin time(PT) and activated partial thromboplastin time(APTT) in mice in the low-and high-dose(5, 30 g·kg~(-1), respectively) Trichosanthis Semen, the shell, and kernel groups were determined as the coagulation markers. The spectrum-effect relationship and anticoagulant material basis of Trichosanthis Semen and its shell and kernel were analyzed with mean value calculation method of Deng's correlation degree(MATLAB) and the common effective component cluster was obtained. Then the common targets of the component cluster and coagulation were retrieved from TCMSP, Swiss-TargetPrediction, GenCLiP3, GeneCards, and DAVID, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. The main anticoagulant molecular mechanism of the component cluster was verified by SYBYL-X 2.1.1. The spectrum-effect relationship of Trichosanthis Semen and its shell and kernel was in positive correlation with the dosage. The contribution of each component to anticoagulation was not the same, suggesting that the material basis for anticoagulation was different, but they have common effective components(i.e. common material basis), such as adenine(peak 3), uracil(peak 4), hypoxanthine(peak 6), xanthine(peak 9), and adenosine(peak 11). Network pharmacology showed that these components can act on multiple target proteins such as NOS3, KDR, and PTGS2, and exert anticoagulant effect through multiple pathways such as VEGF signaling pathway. They involved the biological functions such as proteolysis, cell component such as cytosol, and molecular functions. The results of molecular docking showed that the binding free energy of these components with NOS3(PDB ID: 1 D0 C), KDR(PDB ID: 5 AMN), and PTGS2(PDB ID: 4 COX) was ≤-5 kJ·mol~(-1), and the docking conformations were stable. Spectrum-effect relationship-integrated molecular docking can be used for the optimization, virtual screening, and verification of complex chemical and biological information of Chinese medicine. Trichosanthis Semen and its shell and kernel have the common material basis for anticoagulation and they exert the anticoagulant through multiple targets and pathways.


Subject(s)
Animals , Anticoagulants/pharmacology , Drugs, Chinese Herbal/pharmacology , Gene Ontology , Mice , Molecular Docking Simulation , Semen
2.
Article in Chinese | WPRIM | ID: wpr-275431

ABSTRACT

To explore the effect of Shuxuetong injection on the pharmacodynamics and pharmacokinetics of warfarin in rats, and to provide reference for rational drug use. In studies on the single dose of warfarin, Wistar rats were randomly divided into four groups: blank control group(group A), Shuxuetong injection group(group B), warfarin control group(group C), and warfarin+Shuxuetong injection group(group D). In studies on the steady state of warfarin, Wistar rats were randomly divided into warfarin control group(group E) and warfarin+Shuxuetong injection group(group F). To investigate the pharmacodynamic effect of Shuxuetong injection on warfarin, prothrombin time(PT) and activated partial thromboplastin time(APTT) were measured by coagulation analyzer, and international normalized ratio(INR) was calculated. To investigate the pharmacokinetic effect of Shuxuetong injection on warfarin, the blood concentrations of S-warfarin and R-warfarin were determined by UPLC-MS/MS combined with technology of chiral chromatographic column, and the related pharmacokinetic parameters were calculated accordingly. The results on the single dose of warfarin showed that Shuxuetong injection markedly increased PT, INR(P<0.01), and APTT(P<0.05). Meanwhile, when Shuxuetong injection was co-administrated with warfarin, it significantly increased PT, INR(P<0.01), and APTT(P<0.05) as compared with warfarin control group. In addition, increased pharmacokinetic parameters including Cmax, AUC0-t and AUC0-∞, prolonged t1/2, and decreased CL/F were observed for S-warfarin and R-warfarin. The results of the steady state of warfarin suggested that Shuxuetong injection significantly increased PT and INR of warfarin(P<0.01), and elevated the plasma concentrations of S-warfarin and R-warfarin when co-administrated with warfarin. These findings indicated that Shuxuetong injection had anticoagulant effect, and would produce pharmacodynamics synergistic action when it was co-administrated with warfarin. Shuxuetong injection also decelerated the metabolism of warfarin, and resulted in pharmacokinetics interaction. Therefore, Shuxuetong injection could significantly increase anticoagulant effect of warfarin, indicating that the combination use of these two drugs should be refrained in order to avoid the risk of bleeding in clinical application. If they need to be used in combination, special attention should be paid to ensure the safety of patients.

3.
Article in English | WPRIM | ID: wpr-71717

ABSTRACT

This study aimed to explore the correlation between usual vitamin K intake and response to anticoagulant therapy among patients under warfarin therapy. We conducted a retrospective survey of patients (n = 50) on continuous warfarin therapy. Clinical information and laboratory parameters were sourced from medical records. Anticoagulant effect was evaluated by using the percent time in therapeutic range (TTR) and the coefficient of variation (CV) of International normalized ratio (INR). Dietary vitamin K intake was assessed using a semi-quantitative food frequency questionnaire that has been developed for the purpose of assessing dietary intake of vitamin K. A total of 50 patients aged between 21 and 87 years were included in the study. The mean vitamin K intake was 262.8 +/- 165.2 microg/day. Study subjects were divided into tertiles according to their usual vitamin K intake. The proportion of men was significantly higher in second and third tertile than first tertile (p = 0.028). The mean percent TTR was 38.4 +/- 28.4% and CV of INR was 31.8 +/- 11.8%. Long-term warfarin therapy group (> or = 3 years) had a higher percentage of TTR as compared to the control group ( 0.05). In conclusion, no significant association was observed between usual vitamin K intake and anticoagulant effects. Further studies are required to consider inter-individual variability of vitamin K intake. Development of assessment tools to measure inter-individual variability of vitamin K intake might be helpful.


Subject(s)
Humans , International Normalized Ratio , Male , Medical Records , Retrospective Studies , Vitamin K , Vitamins , Warfarin
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