Abstract:

To investigate the pharmacokinetics of effective components of Bu Yang Huang Wu Decoction (BYHWD) with different dosages of Astragalus (Yiqi groups and Huoxue groups ) applicating in rats with middle cerebral artery occlusion (MCAO). Replicating the animal model of cerebral ischemia-reperfusion in rats, establishing the liquid-mass spectrometry method for the determination of BYHWD and researching the pharmacokinetics of effective components of yiqi groups of BYHWD with different dosages of astragalus (3.09, 6.17, 12.34 g/Kg) and Huoxue goups (2.32 g/Kg) when applicated seperately in the rats suffering from cerebral ischemia reperfusion injury after femoral vein administration. The pharmacokinetics of formononetin and paeoniflorin in the different dosage groups of BYHWD met the one-compartment model, and the t_1/2 of formononetin and paeoniflorin in the low-dose Yiqi and Huoxue groups were (88.43±3.82, 69.18±0.11) min,  MRT were (138.56±4.83, 113.62±2.42) min, and AUC_0–t were (28 488.35±4800.32, 140 614.80±23 954.05) ng/mL·min; The t_1/2 of formononetin and paeoniflorin in the middle-dose Yiqi group and Huoxue group were (82.16±1.78, 67.08±3.69) min, and MRT were (127.95±2.70, 116.58±4.13), AUC_0–t were (48 619.25±6745.75, 159 026.00±15 003.33) ng/mL·min; The t_1/2 of formononetin and paeoniflorin in the high-dose Yiqi and Huoxue groups were (80.29±1.12, 69.69±0.87) min, and MRT was (128.79±1.46, 118.78±4.56) min, AUC_0–t were (109 942.90±13 101.83, 189 417.90±22 311.00) ng/mL·min. The concentration rate of formononetin t_{1/2 brain} was decreased with increase of Astragalus dose. However, no significant difference between these two variables was found during experiments. Furthermore, the experiments showed that the increasing dose of astragalus would affect the pharmacokinetic behavior of paeoniflorin in the Huoxue groups. More specifically, the result showed that paeoniflorin can be metabolized more slowly in the body when applicated in high dose of the jaundice administration groups . In this way, the effect of paeoniflorin can be lasted for longer time in the body and brain.

Key words: Bu Yang Huan Wu Tang, Pharmacokinetics, Microdialysis, Cerebral ischemia-reperfusion