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May 27, 2026PharmaceuticalsOpen Access

Zhi-Zi-Chi Decoction Alleviates Depressive-like Behaviors by Regulating Gut Microbiota and Targeting the AMPK/PI3K-TOR Pathway via Its Metabolite Protocatechuic Acid

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Authors

XJXue JiangJYJicheng YangYZYing Zhang

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Overview

Randomized trial finds Zhi-Zi-Chi Decoction improves depression-like behaviors in mice, suggesting novel therapeutic pathways.

Key Points

  • This study investigates the effects of Zhi-Zi-Chi Decoction on chronic restraint stress-induced neurodysfunction in mice and explores underlying mechanisms.
  • Mice underwent chronic restraint stress and were treated with Zhi-Zi-Chi Decoction or protocatechuic acid.
  • Behavioral tests assessed depression- and anxiety-like behaviors.
  • 16S rRNA sequencing and untargeted metabolomics analyzed gut microbiota and metabolite changes.
  • ZZCD significantly reversed CRS-induced depression- and anxiety-like behaviors.
  • ZZCD treatment altered gut microbiota, reducing Prevotella and increasing Lactobacillus.
  • ZZCD normalized the PI3K/Akt/mTOR pathway and activated AMPK, promoting M2 microglial polarization.

Cite This Study

Jiang et al. (2026) studied this question.

synapsesocial.com/papers/6a16898b0c924ddd1bd5839dhttps://doi.org/10.3390/ph19060819
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

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  4. 4Zhi‐zi‐chi decoction mitigates depression by enhancing lncRNA Six3os1 expression and promoting histone H3K4 methylation at the BDNF promoter2024 · 8 citations
  5. 5Molecular Mechanisms of Zhizhu Kuanzhong Capsule in the Treatment of Co-Morbid Anxiety and Depression of Functional Dyspepsia: Network Pharmacology, Molecular Docking and In Vivo Validation2026