To identify the chemical differences which lead to the different therapeutic effects of dried rehmannia root(DRR)and prepared rehmannia root(PRR),we compared the chemical composition of decoctions of randomly purchased DRR and PRR using ultra performance liquid chromatography(UPLC)coupled with time-of-fight mass spectrometry and high performance liquid chromatography(HPLC)coupled with evaporative light scattering detection(ELSD)with the aid of multivariate statistical analysis.Both approaches clearly revealed compositional and quantitative differences between DRR and PRR.UPLC-MS data indicated stachyose,rehmaiono-side A(or rehmaionoside B),acteoside(or forsythiaside,or isoacteoside),6-O-coumaroylajugol(or 6-O-E-feruloylajugol,or 6-O-Z-feruloylajugol)as important discriminators between DRR and PRR decoctions.HPLC-ELSD analysis showed that the content of fructose in the decoctions of PRR was about four times greater than that of DRR(P<10^(-5)),while sucrose content in the decoctions of PRR was only about one seventh of that in DRR(P<0.01).Our results suggest that some compounds,such as fructose,stachyose and rehmaionoside,may be responsible for the differing therapeutic effects of DRR and PRR.Furthermore,improvements in quality control for PRR,which is currently lacking in the Chinese Pharmacopoeia,are recommended.
Ferulic acid(FA) is an active component of herbal medicines. One of the best documented activities of FA is its antioxidant property. Moreover, FA exerts antiallergic, anti-inflammatory, and hepatoprotective effects. However, the metabolic pathways of FA in humans remain unclear. To identify whether human CYP or UGT enzymes are involved in the metabolism of FA, reaction phenotyping of FA was conducted using major CYP-selective chemical inhibitors together with individual CYP and UGT Supersomes. The CYPand/or UGT-mediated metabolism kinetics were examined simultaneously or individually. Relative activity factor and total normalized rate approaches were used to assess the relative contributions of each major human CYPs towards the FA metabolism. Incubations of FA with human liver microsomes(HLM) displayed NADPH-and UDPGA-dependent metabolism with multiple CYP and UGT isoforms involved. CYPs and UGTs contributed equally to the metabolism of FA in HLM. Although CYP1 A2 and CYP3 A4 appeared to be the major contributors in the CYP-mediated clearance, their contributions to the overall clearance are still minor(< 25%). As a constitute of many food and herbs, FA poses low drug-drug interaction risk when co-administrated with other herbs or conventional medicines because multiple phase I and phase II enzymes are involved in its metabolism.
