Correlation study on in vivo pharmacokinetics and anti-oxidation of Guhong Injection in cerebral ischemia reperfusion injury model of rats / 中草药

ABSTRACT

Objective: To investigate the in vivo pharmacokinetic progress of hydroxysafflor yellow A (HSYA) from Guhong Injection in cerebal ischemia reperfusion (I/R) injury of rats and the correlation with its anti-oxidation effect. Methods: The equilibrium dialysis method was carried out to determine the plasma protein binding rates of HYSA and HSYA in Guhong Injection. Middle cerebral artery occlusion (MCAO) model rats were iv injected HYSA (4 mg/kg) or Guhong Injection (10 mL/kg). The HPLC method was adopted to determine the plasma concentration of HYSA at different time points to draw the drug-time curve. Meanwhile, glutathione peroxidase (GSH-Px) and lactate dehydrogenase (LDH) activities were determined to draw the time-effect curve. Furthermore, the relationship between pharmacokinetics and pharmacodynamics was analyzed. Results: At the concentration of 2.5, 10, and 25 mg/L, the p plasma rotein binding rates of HYSA were 77.96%, 73.54%, and 76.13%, whereas the plasma protein binding rates of HYSA from Guhong Injection were 68.21%, 58.22%, and 63.17%, respectively. A good linear relationship of HYSA was obtained in the range of 0.01-50 mg/L, the mean recoveries were (99.94 ± 2.82)%, (104.16 ± 1.41)%, and (99.74 ± 1.06)% for low, middle, and high concentration of the samples, respectively. Compared with HYSA group, Guhong Injection significantly increased the AUC of HYSA and decreased the MRT and Vz of HYSA. Furthermore, Guhong Injection increased the content of GSH-Px and decreased the content of LDH. The plasma concentration of HYSA is positively related to the GSH-Px activity and negatively related to the LDH activity. Conclusion: The results indicate that HYSA has the moderate plasma protein binding rate. Compared with HYSA group, the plasma protein binding rate in Guhong Injection group is reduced. Guhong Injection could increase the bioavailability of HYSA to enhance therapeutic efficacy and increase the distribution of HYSA in ischemia rats. Guhong Injection has better anti-oxidant effect, as well as more significant protective effect against cerebral I/R injury than HYSA.