Chemical-pharmacokinetic-pharmacodynamic fingerprints of Schisandra chinensis alcoholic extract.

It is valuable to establish a chemical-pharmacokinetic (PK)-pharmacodynamics (PD) fingerprint of traditional Chinese medicine (TCM) for comprehensively understanding the TCM integrated conception and revealing the material foundation. The chemical, metabolic in vitro, and PK/PD in vivo fingerprints of Schisandra chinensis (SC) alcoholic extract were established and comparatively analyzed using HPLC-UV-MS method, rat liver microsomes in vitro and CCl4 intoxicated rats in vivo. Four known effective lignans, schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin, were detected as the standard references in SC alcoholic extract with high concentration. SC alcoholic extract and four lignans when incubated with rat liver microsomes produced several metabolites in NAPDH-dependent manner. Chemical fingerprint of some components with bioactivities were also identified in PK and PD fingerprints in normal and ALI rats that explained the material foundation of SC alcoholic extract for multiple pharmacological effects. Schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin could be considered as the "PK marker" of SC alcoholic extract or its relevant preparations, while two metabolites of the four lignans, 7, 8-dihydroxy-schizandrin and another one (M(W) 432), could be recognized as drug-metabolism (DM) Marker. This work provides experimental data for the further studies of metabolism or material foundation of SC components.