Objective: The aim of our research was to analyze and compare the pharmacokinetics of paeoniflorin, calycosin, calycosin-7-o-β-d-6-glucoside, and 6-gingerol in the blood and brain tissue of normal and cerebral ischemia-reperfusion injury rats by HPLC-MS/MS method.
Methods: The blood and brain tissue samples of normal and middle cerebral artery occlusion (MCAO) rats were compared. The blood and brain tissue samples were collected by using microdialysis technique. The concentrations of paeoniflorin, calycosin, calycosin-7-o-β-d-6-glucoside, and 6-gingerol in blood and brain tissues were determined by the HPLC-MS/MS internal standard method.
Results: Compared with the normal group, the model group after the administration of the Huangqi Guizhi Wuwu Decoction showed that C_{max blood}, AUC_{0-t blood}, and AUC_{0-inf blood} of paeoniflorin were increased, CL_blood, t_{1/2 brain}, and V_brain of paeoniflorin were decreased; C_maxblood, AUC_0-tblood, AUC_0-infblood, and average residence time (MRT_brain) of calycosin-7-o-β-d-6-glucoside were decreased and the CL_blood and C_{max brain} of calycosin-7-o-β-d-6-glucoside were increased; C_{max blood} of calycosin was decreased, V_blood and V_brain of calycosin were increased; C_{max blood}, AUC_{0-t blood}, AUC_{0-inf blood}, and MRT_brain of 6-gingerol were decreased, CL_blood of 6-gingerol was increased.
Conclusion: This method is simple, rapid, and sensitive. It is suitable for the pharmacokinetic study of Huangqi Guizhi Wuwu Decoction in the blood and brain tissue of rats. Cerebral ischemia-reperfusion injury increased the content of paeoniflorin, calycosin, calycosin-7-o-β-d-6-glucoside, and 6-gingerol in the blood, affecting the clearance rate of paeoniflorin in the brain, the detention time of calycosin-7-o-β-d-6-glucoside and the 6-gingerol in the brain. In normal and cerebral ischemia-reperfusion rats, the content of paeoniflorin and 6-gingerol in the blood was higher than that in brain tissue, while the content of calycosin, calycosin-7-o-β-d-6-glucoside in the brain tissue was higher than that in blood, suggesting that calycosin and calycosin-7-o-β-d-6-glucoside have brain targeting properties.
Keywords: Huangqi Guizhi Wuwu Decoction, microdialysis, paeoniflorin, calycosin-7-o-β-d-6-glucoside, calycosin, 6-gingerol, pharmacokinetics