Shao-Ma-Zhi-Jing granules alleviate Tourette Syndrome by modulating the cAMP/PI3K/AKT/NF-κB signaling pathway, T cell differentiation, microglia, and gut microbiota.

INTRODUCTION

Shao-Ma-Zhi-Jing Granules (SMZJ) is clinically used for Tourette syndrome (TS). This study aimed to investigate the regulatory effects of SMZJ on the immune system and gut microbiota of the 3,3'-iminodipropionitrile (IDPN)-induced TS rat model.

METHODS

Immune-related indicators were detected by flow cytometry, western blotting, ELISA and qRT-PCR. Gut microbiota composition was analyzed via 16S rDNA sequencing, and Spearman analysis was performed to assess the correlation between gut microbiota and immune function.

RESULTS

SMZJ suppressed IDPN-induced stereotypical behaviors. Furthermore, SMZJ regulated the mRNA and protein levels of T helper 1 (Th1), Th2, Th17, and T regulatory (Treg) cell-related transcription factors and modulated Th1 and Th2 cytokines in the TS rat model. SMZJ downregulated the inflammatory pathway in the brain striatum, the TNF-α and IL-6 (inflammatory cytokines) levels, and the striatal iNOS levels in the TS rat model. The diversity and structure of the gut microbiota were remodeled using the SMZJ-treated TS rat model. SMZJ modulated the correlation between immune parameters and gut microbiota.

CONCLUSIONS

SMZJ alleviated peripheral and neuroinflammation in TS rats via promoting T cell differentiation and downregulating TNF-α and IL-6 levels, which may be related to changes in the cAMP/PI3K/Akt/NF-κB signaling pathway. SMZJ downregulated the activation of striatal M1 microglia in the TS model. SMZJ may potentially modulated gut microbiota structure and metabolism, relieves peripheral and neuroinflammation, and ameliorates intestinal mucosal barrier injury.