Xiao-Chai-Hu-Tang Ameliorates Depressive Symptoms via Modulating Neuro-Endocrine Network in Chronic Unpredictable Mild Stress-Induced Mice

IF 4.8 1区医学 Q1 NEUROSCIENCES CNS Neuroscience & Therapeutics Pub Date : 2025-02-21 DOI:10.1111/cns.70290

Ying Feng, Wenkai Wang, Yingru Zhang, Yuanyuan Feng, Yiyang Zhao, Zhaozhou Zhang, Yan Wang

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引用次数: 0

Abstract

Objective

Xiao-Chai-Hu-Tang (XCHT) has been demonstrated to exert an antidepressant effect during long-term clinical practices. However, the potential mechanisms of XCHT remain unknown. This study aims to investigate the effect of XCHT on chronic unpredictable mild stress-induced mice with depressive-like behaviors and to explore the underlying mechanisms.

Methods

The active compositions and potential related targets of XCHT in the brain were obtained through UPLC-Q-TOF-MS, network pharmacology, and bioinformatics analyses, verified by experimental validation. Then, the protein–protein interaction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and molecular docking were used to predict the core targets and mechanisms of XCHT on depression. After being treated with XCHT standard decoction, based on enzyme-linked immunosorbent assay (ELISA), non-targeted metabolism, targeted LC–MS analyses, RNA-seq, quantitative RT-PCR, immunofluorescence, and western blotting were determined to clarify the mechanism of XCHT in the treatment of anxiety and depression disorder.

Results

In total, 166 active ingredients and 525 related targets of XCHT were detected and selected from the network databases. The inflammatory response and metabolism of neurotransmitters were the main related signaling pathways predicted by KEGG enrichment analyses. Behavioral testing shows that XCHT has antidepressant effects, and untargeted metabolomic studies showed it significantly reduced levels of the neurotoxic substance quinoline acid. Combining the results of molecular docking, RNA-seq, and western blot revealed that XCHT regulated nerve regeneration via BDNF/TrkB/CREB and PI3K/AKT signaling pathways. Immunofluorescence analysis revealed that XCHT downregulated the chronic stress-induced activation of microglia and astrocytes in the hippocampus.

Conclusion

XCHT exerts antidepressant functions by modulating neuroinflammation and neuroregeneration.

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.