ABSTRACT
OBJECTIVE@#To investigate the effects of the active ingredients combined therapy on inflammatory factors interleukin 1 beta (IL-1β) and neuropeptide Y (NPY) based on pharmacodynamics in rats.@*METHODS@#The animal model was built by transient middle cerebral artery occlusion (MCAO). The method for evaluating the concentrations of the FA-Pr-Al components in rat plasma was established by using HPLC and the expression levels of IL-1β and NPY were determined by ELISA. A new mathematics method of the trend of percentage rate of change (PRC) was used to assess the correlation between pharmacokinetics (PK) and pharmacodynamics (PD).@*RESULTS@#FA-Pr-Al in combination reduced neurological deficits, decreased infarct volume and inhibited the expression levels of IL-1β and NPY (all P<0.05) compared with the model group. FA, Pr and Al all displayed two compartment open models in rats. Clockwise hysteresis loops were obtained by time-concentration-effect curves. IL-1β and NPY level changes in the plasma followed an opposite trend to the plasma concentration tendency after Cmax was reached. Astragaloside's PRC value was significantly higher than those of FA and puerarin between 120 to 180 min.@*CONCLUSIONS@#The pharmacokinetics of FA-Pr-Al in combination were closely related its pharmacodynamics in treating ischemia/reperfusion injury, and the components of FA-Pr-Al may have a synergistic pharmacological effect. Astragaloside may play a more pronounced role in regulating IL-1βand NPY levels compared with puerarin or FA.
ABSTRACT
Objective: To investigate the effects of the active ingredients combined therapy on inflammatory factors interleukin 1 beta (IL-1β) and neuropeptide Y (NPY) based on pharmacodynamics in rats. Methods: The animal model was built by transient middle cerebral artery occlusion (MCAO). The method for evaluating the concentrations of the FA-Pr-Al components in rat plasma was established by using HPLC and the expression levels of IL-1β and NPY were determined by ELISA. A new mathematics method of the trend of percentage rate of change (PRC) was used to assess the correlation between pharmacokinetics (PK) and pharmacodynamics (PD). Results: FA-Pr-Al in combination reduced neurological deficits, decreased infarct volume and inhibited the expression levels of IL-1β and NPY (all Pmax was reached. Astragaloside's PRC value was significantly higher than those of FA and puerarin between 120 to 180 min. Conclusions: The pharmacokinetics of FA-Pr-Al in combination were closely related its pharmacodynamics in treating ischemia/reperfusion injury, and the components of FA-Pr-Al may have a synergistic pharmacological effect. Astragaloside may play a more pronounced role in regulating IL-1βand NPY levels compared with puerarin or FA.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the absorption characteristics and transportation mechanism Yangyin Tongnao granules in main effective fractions in Caco-2 cell model.</p><p><b>METHOD</b>The safety concentrations of Yangyin Tongnao granules in main effective fractions in Caco-2 cells. A Caco-2 cell model was established to study the transport situations after the compatibility of Yangyin Tongnao granules in main effective fractions, and the content was determined by high performance liquid chromatography (HPLC).</p><p><b>RESULT</b>P(app) of puerarin, ligustrazine and astragaloside were less than 1.0 x 10(-6) cm x s(-1), and their P(app) were hard to be close to atenolol. The oral absorption in descending order is shown as the following: puerarin, ligustrazine, astragaloside. After the compatibility between saponins and flavonoids, P(app) of astragaloside was improved obviously, which promoted the transport from apical (AP) to basolateral (BL); the compatibility of puerarin, ligustrazine and astragaloside showed a significant effect in the efflux of astragaloside and no change in the absorption transport of ligustrazine and puerarin at the same time. There is a great difference in bidirectional transport of representative component of each effective fraction, and P(app)(B --> A) was significantly greater than Papp(A --> B), which suggested that the efflux transport from BL side to AP side had an advantage in the three representative components of the three effective fractions in Caco-2 cell monolayer model.</p><p><b>CONCLUSION</b>Astragaloside, ligustrazine and puerarin may be malabsorptive compounds, and the three compounds may be discharged by the transport protein in small intestine membrane.</p>