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

Abstract

To evaluate the pharmacokinetics of phenolic compounds after oral administration of Danshen extract in rat brain. 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 μL/min, respectively. Blank microdialysates were collected after 2h post-implantation equilibrium time. Danshen extract (danshensu 40 mg/kg BW, protocatechuic aldehyde 149 mg/kg BW, and salvianolic acid B 50mg/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. 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. 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.