Pharmacokinetics of phenolic compounds of Danshen extract in rat blood and brain by microdialysis sampling

Aim of the study: To evaluate the pharmacokinetics of phenolic compounds after oral administration of Danshen extract in rat brain. Materials and methods: Blood and brain microdialysis probes were inserted into jugular vein and cerebral cortex of rat under anesthesia and perfused with ringer's solution at the rate of 2.0 and 0.8 mu L/min, respectively. Blank microdialysates were collected after 2 h post-implantation equilibrium time. Danshen extract (danshensu 40 mg/kg BW, protocatechuic aldehyde 149 mg/kg BW, and salvianolic acid B 50 mg/kg BW) was administrated intragastrically, and then blood and brain microdialysates were collected at 15 and 30 min time intervals for 4h, respectively. The concentrations of phenolic compounds were determined by high-performance liquid chromatography coupled with chemiluminescence detection. Pharmacokinetic parameters were estimated using non-compartmental methods. Results: Danshensu and protocatechuic acid could be detected in both blood and brain microdialysates, while protocatechuic aldehyde and salvianolic acid B were not detected. Brain-to-blood (AUC(brain)/AUC(blood)) distribution ratio were 0.25 +/- 0.04 and 0.09 +/- 0.02 for danshensu and protocatechuic acid, respectively. Conclusions: Danshensu can readily permeate the blood brain barrier after oral administration of Danshen extract, and protocatechuic acid is a potential oxidative metabolite of protocatechuic aldehyde. (C) 2011 Elsevier Ireland Ltd. All rights reserved.