Elucidation of mechanism of Si-jun-zi decoction-induced reversal of spleen deficiency syndrome in rats by LC-Q-TOF/MS metabolomics

Purpose: To explore the therapeutic effect and mechanism of action of Si–jun–zi decoction (SJZD) in rat spleen deficiency syndrome.
Methods: Spleen deficiency syndrome was induced in a rat model with reserpine. Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) and partial least squares-discriminate models (PLS-DA) were used to analyze the difference in global metabolite profile within all groups. Variable importance projection (VIP > 1) and Student’s t–test (p < 0.05) were used for biomarker selection.
Results: Enzymatic results showed that the level of amylase (AMY), pepsin (LPS) and pepsase were significantly lower in the untreated rats than in normal control rats and SJZD group rats (P < 0.05). Histopathological analysis showed there were significant pathological changes in the untreated rats compared with the normal control group and SJZD group rats. PLS-DA score plots of the untreated group rats clustered separately from control rats, whereas SJZD group rats clustered closely to normal control rats. Twenty potential biomarkers, including phospholipid and fatty acids, were screened. The relative content of 20 metabolites showed significant differences in the untreated group compared with control and SJZD groups (p < 0.05). Six potentially perturbed metabolic pathways were found, which might be potential targets pathways for SJZD intervention in spleen deficiency syndrome.
Conclusion: Metabolomics approach is an effective tool for understanding the therapeutic mechanisms of SJZD.

Keywords
Si–jun–zi decoction; Spleen deficiency syndrome; Metabolomics; LC-Q-TOF/MS