ORIGINAL RESEARCH article
Front. Mol. Neurosci.
Sec. Molecular Signalling and Pathways
Exploring the Mechanism of Yin Huo Decoction in PCPA-Induced Depression Mice: A Metabolomics and Network Pharmacology Approach
Yu Zhou 1
Lu Jia LIu 2
Yue Zhang 3
Wen Wen Wang 4
Dan Hong Xu 4
1. Wuxi Higher Vocation and Technical School of Health, Wuxi, China
2. Heilongjiang University of Chinese Medicine, Harbin, China
3. Xuzhou Vocational College of Bioengineering, Xuzhou, China
4. Wuxi Higher Vocational and Technical School of Health, Wuxi, China
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Abstract
This study investigates the therapeutic effects of Yin Huo Decoction (YHD) on a PCPA-induced depression model in mice. The results showed that YHD treatment significantly improved body weight, sucrose preference, and behavior in various tests, such as the forced swim and tail suspension tests. Hippocampal neuron structure and Nissl body integrity were preserved in YHD-treated mice, similar to the effects of fluoxetine. YHD also restored the reduced serotonin (5-HT) levels in the brain of PCPA model mice. Additionally, metabolomic profiling of serum, urine, and brain tissue using Liquid Chromatograph Mass Spectrometer (LC-MS) revealed distinct metabolic disturbances in the PCPA model, which were largely corrected by YHD treatment. Pathway enrichment analysis identified key metabolic pathways, including tryptophan and riboflavin metabolism, as the major targets of YHD in restoring metabolic balance. Furthermore, network pharmacology analysis revealed 156 intersecting targets between YHD and depression-related pathways. These targets were primarily involved in neuroactive ligand-receptor interactions, dopaminergic synapses, and various inflammatory processes, such as TNF signaling and cytokine production. The top identified targets, including AKT1, TNF, IL-6, and EGFR, suggest that YHD may exert its antidepressant effects through the regulation of neuroinflammation, neurotransmitter systems, and cellular signaling pathways. In conclusion, YHD alleviates PCPA-induced depression-like behaviors in mice by modulating serotonin levels, correcting metabolic disturbances, and regulating multiple biological processes, as predicted by metabolomics and network pharmacology. These findings provide a comprehensive understanding of the potential mechanisms underlying YHD's therapeutic effects in treating anxiety and depression.
Summary
Keywords
Depression, mechanism of action, Metabolomics, Network Pharmacology, Yin Huo Decoction (YHD)
Received
15 October 2025
Accepted
22 December 2025
Copyright
© 2025 Zhou, LIu, Zhang, Wang and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Dan Hong Xu
Disclaimer
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