Metabolic profile analysis of Zhi-zi-chi decoction in feces of normal and chronic unpredictable mild stress-induced depression rats based on UHPLC-ESI-Q-TOF-MS/MS and multiple analytical strategies

Zhi-zi-chi decoction (ZZCD) has been verified by clinical application that it has definite curative effects and low side effects on depression. Because it is administered orally, the metabolites of ZZCD in the intestinal tract may influence the curative effects significantly. In this study, UHPLC-ESI-Q-TOF-MS/MS was used in combination with untargeted metabolomics-driven strategy, series product ion filtering and diagnostic fragment ion strategy for acquiring the comprehensive metabolic profile of ZZCD in feces of normal and chronic unpredictable mild stress (CUMS)-induced depression rats after oral administration, while the rat depression model was evaluated by behavior tests and plasma biochemical indices. Finally, a total of 56 compounds, including 35 prototype compounds and 21 metabolites, were identified or tentatively characterized in fecal samples. Among these, ten compounds were sieved as potential chemical markers that would reflect the antidepressant effect of ZZCD, which may offer important information for quality assessment, pharmacokinetic study and clinical security. In conclusion, the metabolic profile of ZZCD in normal and CUMS-induced depression rats would be helpful for the further study of anti-depression material basis and mechanism.