Elucidating the Mechanism of ShaoMaZhiJing Granules for Treating Tourette Syndrome: A Metabolomics- and Proteomics-Based Study

Objective: This study aimed to explore the mechanism of action of ShaoMaZhiJing granules (SMZJ) in the treatment of Tourette syndrome (TS) using metabolomic and proteomic methods. Materials and Methods: Sprague–Dawley rats were divided into five groups: control, model, haloperidol, low-dose SMZJ (SML), and high-dose SMZJ (SMH). The TS model was established by intraperitoneally injecting 3,3’ of iminodipropionitrile (IDPN). After 21 d of administration, stereotypical behaviors were observed, and brain samples were collected. Gas chromatography–time-of-flight mass spectrometry (MS) analysis was performed to analyze the brain metabolites. Furthermore, the differential proteins in the brain were analyzed using isotope-labeled relative and absolute quantitative (iTRAQ™) techniques combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Validation experiments used enzyme-linked immunosorbent assay to measure protein phosphatase 2A (PP2A) levels. Results: Behavioral assessments revealed that the frequency of head raising and circumgyration was significantly lower in the SML group than that in the model group ( P < 0.05), and the frequency of head raising was significantly lower in the SMH group than that in the model group ( P < 0.01). The metabolomic analysis revealed that L-cysteine and uridine levels were downregulated after SMZJ treatment, and these molecules were associated with arginine, proline, taurine, hypotaurine, glutathione, cysteine, and methionine metabolism. Furthermore, iTRAQ analysis revealed that PP2A, proteasome β subunit-3, and thymosin β-4 levels were significantly decreased, whereas transmembrane protein 33 level was significantly upregulated after SMZJ treatment. Validation experiments revealed that PP2A levels returned to normal after SMZJ treatment. Conclusions: Our study suggests that SMZJ improves the symptoms of IDPN-induced TS in rats. SMZJ may regulate the dopaminergic synapses, glutamatergic synapses, glutathione metabolism, and energy metabolism in rats.