ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1645190
This article is part of the Research TopicRodent Model Organisms: Therapeutic Treatments and Drugs Interaction with the Gut Microbiome, Volume IIView all articles
Zhi-zi-chi decoction exerts hypnotic effect through gut-brain axis modulation in insomnia mice
Provisionally accepted
Qianqian Wang
Boyi Zhang
Zixuan Guo
Jiawei Huang
湲湲 牛Junhong HuangYu HuangDandan Guo
Baiyan Wang
Shuying Feng*- Henan University of Chinese Medicine, Zhengzhou, China
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Background: Insomnia, a frequently encountered sleep disorder, boasts a high prevalence rate on a global scale. Currently, Western medications are widely used for its treatment; however, they may cause adverse effects such as dependence and daytime drowsiness. Traditional Chinese medicine (TCM) offers a safer alternative. Zhi-zi-chi Decoction (ZZCD), composed of Fructus gardeniae and fermented soybean, has shown potential in promoting sleep, but its mechanism remains unclear. Methods: A PCPAinduced mice model of insomnia was used to evaluate the therapeutic effects of ZZCD. Behavioral tests, neurotransmitter assays, ELISA for HPA axis and inflammatory markers, 16S rDNA gut microbiota sequencing, and histological analyses of brain and colon tissues were performed. Results: ZZCD significantly improved sleep and reduced anxiety-like behavior. It restored GABA and 5-HT levels while lowering GLU and DA, normalized HPA axis activity, reduced inflammatory cytokines, and increased beneficial gut bacteria such as Ligilactobacillus. Histology confirmed neuroprotective and gut barrier-enhancing effects. Conclusions: ZZCD alleviates insomnia by modulating the gut-brain axis, rebalancing neurotransmitters, and restoring microbial homeostasis. These findings support its use as a safe and effective treatment for insomnia.
Keywords: ZZCD, Zhi-zi-chi decoction, TCM, traditional Chinese medicine, FG, Fructus gardeniae, FS, fermented soybean, HPA, hypothalamic-pituitary-adrenal, CRH, corticotropin-releasing hormone, ACTH, adrenocorticotropic hormone, CORT, cortisol
Received: 11 Jun 2025; Accepted: 14 Jul 2025.
Copyright: © 2025 Wang, Zhang, Guo, Huang, 牛, Huang, Huang, Guo, Wang and Feng. 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: Shuying Feng, Henan University of Chinese Medicine, Zhengzhou, China
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