In Vitro Metabolic Research Of Schisanhenol

ObjectiveTo identify the CYPs involved in Fructus schisandrae and their respectiveroles in the reaction in liver. And also to reveal the metabolic pathway(s) ofschisanhenol in humans and different experimental animals including rat, dogand monkey and to compare the similarities and differences in theirbiotransformation activities on schisanhenol in liver microsomes from variousspecies.MethodsUsing human liver and intestinal microsomes, recombinant CYPs, as wellas experimental animals liver microsomes, combined with UFLC,LC-MS/MS, for metabolic phenotype in vitro.ResultsThe current study characterizes the schisanhenol pathway in human, theliver becomes a major detoxifying tissue for schisanhenol (Vmax,Km and Clintis4.111nmol/min/mg pr,9.173μmol/L and0.448ml/min/mg).Afterschisanhenol was in-cubated with human livermicrosomes,three metaboliteswere isolated by HPLC. A study combined correlation analysis, chemicalinhibition studies, assays with recombinant CYPS and enzyme kineticsindicated that CYP3A4is the main hepatic isoform that metabolizesschisanhenol (Vmax, Km and Clintis3.425nmol/min/mg pr,5.666μmol/L and0.604ml/min/mg). The total microsomal intrinsic clearance values forSchisanhenol obeyed the following order: monkey＞rat> human>dog.Rat, dog and human liver microsomes were applied to evaluate speciesdifferences, and the results showed little difference among the mentionedspecies.ConclusionsThe current study characterizes the schisanhenol pathway in human, theliver becomes a major detoxifying tissue for schisanhenol and CYP3A4isdemonstrated to play an important role. Compare with the biotransformationof schisanhenol by Liver Microsomes from Different Species. It provides vitalinformation to better understand the metabolic behaviors ofFructus Schisandra among various species.