Tandem mass tag-based quantitative proteomic analysis of the liver reveals potential protein targets of Xiaochaihutang in CUMS model of depression

Abstract

Depression is a global mental disorder disease and greatly threatened human health. Xiaochaihutang (XCHT) has been used successfully in treatment of depression for many years in China, but the mechanism is unclear. Using the chronic unpredictable mild stress (CUMS) mice model of depression, the present study aimed to reveal possible antidepressant mechanisms of XCHT from the perspective of liver by analyzing hepatic proteomics in mice. Bioinformatics analysis identified 31 differentially expressed proteins (DEPs), including 5 upregulated and 26 downregulated proteins, between the CUMS model and XCHT groups. The bile secretion pathway was found by KEGG pathway analysis of these DEPs. Four of the 31 differentially expressed proteins, including 2 active proteins involved in bile secretion, carbonic anhydrase 2 (CA2) and cystic fibrosis transmembrane conductance regulator (CFTR), were selected to verify their genes. Four genes (Cyp7a1, Fxr, Shp and Ntcp) related to bile acid synthesis and transport were further investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Both biochemical tests and gene studies demonstrated that CUMS affected bile acid synthesis and transport, while XCHT regulated this pathway. The results indicated that there may be a potential relationship between CUMS induced depression and hepatic injury caused by increased bile acid, and also provide a novel insight to understand the underlying anti-depression mechanisms of XCHT.