Pharmacokinetic and pharmacodynamic analysis of ferulic acid-puerarin-astragaloside in combination with neuroprotective in cerebral ischemia/reperfusion injury in rats.

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.