Mechanisms of Changma Xifeng tablet in alleviating Tourette syndrome via modulation of neurotransmitters, inflammatory responses, and metabolic pathways.

INTRODUCTION

Tourette syndrome (TS) is a common pediatric neurodevelopmental disorder. Changma Xifeng tablet (CMXF), a traditional Chinese medicinal formulation, is widely used clinically for TS but its mechanisms remain unclear. This study aimed to evaluate CMXF's efficacy and explore its action mechanisms via a TS murine model.

METHODS

The chemical constituents of CMXF were analyzed and identified by UPLC-Q-TOF-MS/MS. Sixty male BALB/c mice were divided into 6 groups (CON, MOD, HAL, CMXF-L/M/H). TS models were induced by IDPN injection. Behavioral assessments, ELISA (neurotransmitters/inflammatory cytokines), HE staining (striatal pathology), RT-qPCR/WB (DRD1/DRD2/COMT/MAO-B), and UHPLC-Q-TOF LC-MS (serum metabolomics) were performed.

RESULTS

A total of twenty-one components, including gallic acid, gastrodin, catechin, sibiricose A3, paeoniflorin, parishin B, and tenuifoliside B, were identified in CMXF. From week 4 to week 8, the HAL group and CMXF-H group showed significantly improved behavioral performance compared with the MOD group (F > 1, P < 0.001), presenting a dose-dependent trend. ELISA results revealed that CMXF-H significantly increased the levels of 5-HT in serum and striatum (F > 1, P < 0.001), while decreasing the levels of DA, HVA, NE, IL-1β, and IL-6 in serum (F > 1, P < 0.001). RT-qPCR and WB results indicated that CMXF regulated the mRNA and protein, inhibiting DRD1/DRD2 expressions and inducing COMT/MAO-B expressions. Serum metabolomics analysis identified 398 differentially expressed metabolites, which were mainly involved in lipid metabolism and organic acid metabolism pathways.

DISCUSSION: CMXF exerts anti-TS effects by regulating neurotransmitters, inflammatory cytokines, DA signaling, and serum metabolites, providing novel insights into its mechanisms and potential targeted therapy for TS.