ChangPu YuJin Tang improves Tourette disorder symptoms by modulating amino acid neurotransmitters in IDPN model rats.

INTRODUCTION: Changpu Yujin Tang(CPYJT), a Chinese herbal compound, is an effective therapeutic strategy for pediatric patients with Tourette disorder (TD). Therefore, this work aims to investigate the therapeutic mechanisms of CPYJT. METHODS: Behavioral and cellular ultrastructural evaluation of the therapeutic effects of CPYJT in TD model rats. Colorimetric methods, reverse transcription­quantitative PCR, and Western Blot were used to measure the altered levels of GLU, GABA, and the levels of VGLUT1, GLUD1, GABRA3, and GAD65 in the cortex, striatum, and thalamus of the TD model rats after 7, 14, 21, and 28 days of CPYJT administration. RESULTS: CPYJT significantly reduced stereotypic behavior and motor behavior scores in TD model rats. CPYJT ameliorates myelin structural damage in TD model rat neuronal cells. CPYJT decreased GLU content, elevated GABA content, decreased GLUD1 and VGLUT1 levels, and elevated GAD65 and GABRA3 levels in TD model rats' cortex, striatum, and thalamus. CPYJT has different regulatory time points in the cortex, striatum, and thalamus for critical factors of amino acid-based neurotransmission. CONCLUSION: CPYJT protects behavioral and structural damage of neuronal cells in multiple brain regions in TD model rats.

Network Pharmacology Combined with Animal Models to Investigate the Mechanism of ChangPu YuJin Tang in the Treatment of Tourette Syndrome.

BACKGROUND: ChangPu YuJin Tang (CPYJT) is a Chinese herbal formula that has been shown to be an effective therapeutic strategy for pediatric patients with Tourette Syndrome (TS). Using an integrated strategy of network pharmacology and animal model, the aim of this study was to investigate the mechanism of CPYJT in the treatment of TS. METHODS: Compound libraries of CPYJT were established using databases, such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The TCMSP database and Swiss Target Prediction database were used to predict the targets. The above results were constructed into a CPYJT-Drug-Component-Target network. Moreover, TS targets were predicted using GeneCards and other databases. The targets corresponding to the potential ingredients in CPYJT and the targets corresponding to TS were taken as the intersections to construct the CPYJT-TS network. The target network was analysed by PPI using the string database. GO and KEGG enrichment analyses were performed on the target network. The whole process was performed using Cytoscape 3.7.2 to make visual network diagrams of the results. CPYJT was characterised by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS). Transmission Electron Microscopy (TEM) was used to observe the structural changes of CPYJT on the neuronal cells of the IDPN model rats. RT-PCR and Western Blot were used to analyse the changes in the mRNA and protein expression levels of BDNF, TrkB, PI3K, and AKT in the cortex, striatum, and thalamus brain regions after CPYJT administration in IDPN model rats. RESULTS: Network pharmacology and UHPLC-MS studies revealed that CPYJT acted on the TS through multiple neurotransmitters and the BDNF/TrkB and PI3K/AKT signalling pathways. CPYJT ameliorated neurocellular structural damage in the cortex, striatum, and thalamus of TS model rats. Additionally, CPYJT up-regulated the levels of BDNF, TrkB, PI3k, and AKT in the cortex, striatum, and thalamus of TS model rats. CONCLUSION: It was found that CPYJT protected neuronal cells from structural damage in multiple brain regions and affected the expression levels of BDNF, TrkB, PI3K, and Akt in the cortex, striatum, and thalamus during TS treatment.