A preliminary study on the effects of Xiaoyao San on neurological function and 5-HT2A mRNA expression in mice with Tourette syndrome

Background

Tourette syndrome (TS) is a chronic neuropsychiatric disorder, also known as multiple tic syndrome. TS is associated with the serotonin (5-HT) system, of which 5-HT2A is a subtype. Xiaoyao San (XYS) comes from “Prescriptions of the Bureau of Taiping People’s Welfare”. It has the effect of harmonizing liver and spleen, relieving depression, nourishing blood, and invigorating spleen. However, the therapeutic mechanism of XYS for TS has not been evaluated. This study aimed to investigate the therapeutic effect of XYS on the TS mouse model and its possible mechanism.

Methods

A mouse model of TS induced by DOI (selective 5-HT (2A/2C) receptor agonist, 10 ml/kg) was established. The mice were randomly divided into normal control group, DOI group, DOI + Tiapride Hydrochloride (Tia at 25 mg /kg) group, DOI + XYS low-dose (1.44 g/kg/d), medium-dose (2.88 g/kg/d) and high-dose (5.76 g/kg/d) groups, and the mice were given the corresponding drug intragastric administration for four consecutive weeks, and the stereotypic behavior was recorded weekly. The morphological characteristics of the cells were observed by hematoxylin–eosin staining. The content of 5-HT was determined by enzyme-linked immunosorbent assay. Western blot and quantitative polymerase chain reaction were used to detect 5-HT2A.

Results

XYS could significantly improve the stereotypic behavior of TS mice, and the improvement effect increased with the increase of dose, the improvement effect of XYS high dose was similar to that of Tia. After Tia or XYS high-dose treatment, the prefrontal cortex cells and neuronal structure of TS mice gradually normal, cells arranged neatly. The prefrontal cortex cells recovered generally after XYS low-dose and medium-dose treatments. 5-HT in the serum of mice in all treatment groups was higher than that in the DOI group, and 5-HT in serum of XYS high-dose group and Tia group was the highest. 5-HT2A receptor protein and mRNA in the prefrontal cortex of mice in all treatment groups showed a downward trend, and the decrease degree was the largest in the XYS high-dose group and Tia group.

Conclusion

XYS has an improvement effect on TS in mice, and its mechanism is related to reducing 5-HT2A receptor expression, increasing 5-HT content, and enhancing 5-HT system activity. These results suggest that XYS is a therapeutic strategy for TS treatment.