Xiao-Er-An-Shen Granule inhibits dopamine production to ameliorate Tourette syndrome in mice

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-09-09 DOI:10.1016/j.phymed.2025.157243

Lifang Wei , Changhui Li , Daozheng Fang , Chi Zhang , Haipiao Huang , Jinru Wu , Lin Zheng , Yinghao Yin , Qiugu Chen , Shiying Huang , Jihang Chen , Jianping Chen

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引用次数: 0

Abstract

Background

Tourette syndrome (TS) is a neuropsychiatric disorder that typically manifests in childhood. Currently, anti-psychotic drugs that aim to reduce dopaminergic hyperinnervation in the brain are recommended for TS. These drugs have been proven to increase the risk of extrapyramidal symptoms, which hinder their use. Gut microbiota has been shown to modulate dopamine (Da) metabolism along gut-brain axis and be relevant to the development of TS, and which may be a novel strategy for TS therapy. Xiao-Er-An-Shen Granule (XEASG) is a clinically prescribed herbal mixture that has demonstrated clinical efficacy in treating TS. The detailed mechanism of XEASG in alleviating TS symptoms through the gut-brain axis however remains incompletely understood.

Purpose

This study aimed to investigate the effect of XEASG on TS through regulating Da synthesis both in the brain and gut microbiota.

Methods

XEASG at doses of 2 and 4 g/kg/d was administered orally to 3,3′-iminodipropionitrile (IDPN)-induced TS model mice. Behavioral assessments, targeted metabolomics analysis, 16S rRNA sequencing and enzyme-linkedimmunosorbent assay (ELISA) were employed to elucidate the therapeutic effects and mechanisms of XEASG for TS treatment.

Results

Data showed that XEASG treatment significantly alleviated IDPN-induced tic-like behavior in mice. XEASG significantly reduced Da level in the brain tissues of TS mice, resulting from down-regulated Da synthesis but up-regulated Da degradation. Aberrant Da metabolism was also found in serum and colon contents of TS mice, which was restored by XEASG treatment. Furthermore,16S rRNA sequence revealed that XEASG altered the microbial community composition. Finally, experimental validation confirmed that XEASG suppressed Da synthesis pathway by reducing tyrosine hydroxylase level in the gut microbiota.

Conclusion

Our findings reveal that XEASG alleviates TS via inhibiting Da synthesis in the brain and gut, which suggests that the regulation of Da through gut microbiota by XEASG could be a therapeutic strategy for TS treatment.

Abstract Image

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小二安神颗粒抑制多巴胺产生改善小鼠妥瑞特综合征

背景图雷特综合征（TS）是一种典型表现于儿童期的神经精神疾病。目前，旨在减少大脑多巴胺能神经亢进的抗精神病药物被推荐用于TS，这些药物已被证明会增加锥体外系症状的风险，这阻碍了它们的使用。肠道菌群调节多巴胺（Da）沿肠-脑轴代谢，与TS的发展有关，可能是TS治疗的新策略。消儿安肾颗粒是临床上具有临床疗效的中药复方，但其通过肠脑轴缓解TS症状的具体机制尚不完全清楚。目的探讨XEASG通过调节脑和肠道菌群Da合成对TS的影响。方法以2、4 g/kg/d剂量给药3,3′-亚氨基二丙腈（IDPN）诱导的TS模型小鼠。采用行为学评估、靶向代谢组学分析、16S rRNA测序和酶联免疫吸附试验（ELISA）研究XEASG治疗TS的疗效和机制。结果数据显示，XEASG治疗可显著减轻idpn诱导的小鼠抽搐样行为。XEASG显著降低TS小鼠脑组织中Da水平，其机制是下调Da合成，上调Da降解。经XEASG处理后，TS小鼠的血清和结肠内容物Da代谢也出现异常。此外，16S rRNA序列显示XEASG改变了微生物群落组成。最后，实验验证证实XEASG通过降低肠道菌群中的酪氨酸羟化酶水平来抑制Da合成途径。结论XEASG通过抑制脑和肠道Da合成来缓解TS，提示XEASG通过肠道菌群调节Da可能是治疗TS的一种治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.