Label-free mass spectrometry-based proteomics for investigating the therapeutic mechanism of Sijunzi decoction on spleen deficiency syndrome

A classic prescription in traditional Chinese medicine, Sijunzi decoction is widely used to treat spleen deficiency syndrome. However, the therapeutic mechanisms are not yet well understood. In this study, the therapeutic effects of Sijunzi decoction were assessed by histopathological examination and enzyme activity analysis (succinate dehydrogenase (SDH) and lactic dehydrogenase (LDH)). A label-free proteomics method was used to assess the changes in the endogenous protein and to explore the action mechanisms of Sijunzi decoction. The screened differentially expressed proteins (DEPs) were analyzed using bioinformatics methods. The results showed Sijunzi decoction could significantly restore damaged liver tissue and enzymatic activities. DEPs of Sijunzi decoction-intervened spleen deficiency syndrome mainly regulated various metabolic processes involved in cellular responses to enzyme activity for catalyzing, transforming and transferring. The four pathways (bile secretion, pyruvate metabolism, cysteine and methionine metabolism, and fatty acid metabolism) might be closely related with the intervention mechanism of Sijunzi decoction on spleen deficiency syndrome. Protein H2afx (H2AFX), interferon stimulated gene 15 protein (ISG15), and signal transducers and activators of transcription1 (STAT1) proteins were predicted to play the important roles in Sijunzi decoction action networks. Our study provides novel perspectives for revealing the therapeutic mechanisms of Sijunzi decoction on spleen deficiency syndrome.