Metabolomics analysis reveals the mechanisms of the effect of Sijunzi decoction on spleen deficiency syndrome in a rat model

Sijunzi decoction (SJZD) is a traditional Chinese medicine prescription which is used to treat spleen deficiency syndrome. Its mechanism of action was studied in a rat model of reserpine-induced spleen deficiency syndrome with metabolomics assays performed in normal control, model and Sijunzi decoction treated rats by liquid chromatography quadruple-time-of-flight mass spectrometry (LC-Q/TOF-MS). Enzyme assays and histopathology, with multivariate statistical analysis, showed that Sijunzi decoction was an effective intervention in model rats. Principal component analysis (PCA) revealed that the metabolite profiles of the model rats and normal control rats were completely separated, and that the profile of the Sijunzi decoction treated rats was similar to that of normal controls. Eighty potential biomarkers of Sijunzi decoction treatment were screened. The most relevant metabolic pathways were glycerophospholipid metabolism, elongation of fatty acids in mitochondria, synthesis and degradation of ketone bodies, fatty acid metabolism, ether lipid metabolism, synthesis of strontium scaffold, praline, degradation of leucine and isoleucine, and metabolism of methyl butyrate. An interaction network of metabolic pathways associated with potential biomarkers was constructed. Then, three potential target molecules of Sijunzi decoction intervention spleen deficiency syndrome including acetyl-CoA, 3-hydroxy-3-methylglutaryl-CoA and hexanoyl-CoA were screened. This study revealed the mechanism of Sijunzi decoction for the treatment of spleen deficiency syndrome and provided a theoretical basis for the clinical application of Sijunzi decoction.