Program

PO1-11-39

Pharmacokinetic evaluation of Xiaoxuming decoction for anti-cerebral ischemic stroke and its protection mechanism in blood-brain barrier

[Speaker] Zhihong Yang:1
[Co-author] Yuyang You:2
1:Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, China, 2:Beijing Institute of Technology, China

Under the traditional Chinese medicine (TCM) theories, Xiaoxuming decoction (XXMD), the classic TCM prescription, had been with systematic pharmacodynamic studies granted by National Natural Science Foundation. Then the further research on pharmacokinetic profile by the weight mode of pharmacological action factor had been done.
The studies were focused on the systematic pharmacokinetic mode for TCM prescription study in brain, via investigated the pharmacokinetic profiles of active ingredient group (31 components detected) of XXMD, evaluated the weight factor (6 cellular energy-metabolism substances) for pharmacological action (anti-cerebral ischemic stroke), then developed the mathematics models to reveal the pharmacokinetic characteristics of the integrity composition of XXMD.
During the studies, the gerbil pathological and physiological self-control brain regions model and the real-time microdialysis technique were applied in order to determine and assay the samples from brain regions dynamically and continuously in the periods of ischemia, reperfusion and recovery.
Furthermore, the studies illuminated the protective effect and molecular mechanism of blood-brain barrier (BBB) against ischemic brain injury. The anti-ischemia effect of XXMD presented by protecting the physical membrane barrier system (permeability and tight junction protein ZO-1, occludin and claudin-5), efflux transporter system (especially including P-GP transporter, BCRP transporter and MRP2 transporter) of the BBB, and regulating the proteins by PKA and PKC signal pathway in BBB endothelial cell. Via studying the effective components (including prototype drugs, metabolites and adduct products), we attempted to elucidate the reasonable and scientific TCM compatibility theories from the aspect of pharmacokinetic characteristics and pharmacodynamic molecular mechanism of XXMD.
Acknowledgements: This work was supported by grants from National Natural Science Foundation of China (81473579, 81273654 and 81102879), Beijing Natural Science Foundation (7173267), and National Science and Technology Major Projects for "Major New Drugs Innovation and Development" (2013ZX09103002-022).
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