Serum metabolomics reveals compatibility rules of the antidepressant effects of Xiaoyaosan and its efficacy groups.

Abstract Traditional Chinese medicines (TCMs) have attracted more attentions in the treatment of depression. Xiaoyaosan (XYS), a classic anti-depression TCM prescription, contains eight herbs. However, the compatibility effects of XYS in modern pharmacology need to be investigated in depth. In this study, the chronic unpredictable mild stress (CUMS) depression-like model was constructed. Then, XYS was divided into the Shugan and the Jianpi groups according to the research strategy of Efficacy Groups. Meanwhile, a proton nuclear magnetic resonance spectrometry (1H NMR) based serum metabolomics was applied. XYS and its efficacy groups significantly regulated the abnormal levels of differential metabolites related to depression, but to different degrees. Metabolic profiling by orthogonal partial least squares discriminant analysis showed that XYS at high dose (XH) exhibited the strongest effects than other treatment groups. Ten metabolites related to depression were identified as differential metabolites. Besides, relative distance (Rd) was calculated to quantitatively evaluate the effects. We found that XH group had the highest Rd value. Moreover, among the five metabolic pathways of depression, XYS and Jianpi groups significantly regulated all pathways while Shugan group regulated four pathways. These findings lay a solid foundation for comprehensively and deeply understanding the compatibility effects of XYS against depression.