The depressive-like behaviors of chronic unpredictable mild stress-treated mice ameliorated by Tibetan medicine Zuotai: involvement in the hypothalamic–pituitary–adrenal (HPA) axis pathway
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BACKGROUND: Zuotai, a famous Tibetan medicinal mixture containing metacinnabar, is traditionally used for the purpose of tranquilizing minds and soothing nerves. However, it still lacks substantial experimental data for it to be approved for use. AIM: This study was designed to assess the effects of Zuotai on depressive-like symptoms in a chronic unpredictable mild stress (CUMS) mouse model, and to explore its potential mechanism, particularly the hypothalamic-pituitary-adrenal (HPA) axis pathway. MATERIALS AND METHODS: First, Kunming mice were exposed to the CUMS procedure and simultaneously administered Zuotai or imipramine (positive control) by gavage continuously for 6 weeks. Then, depressive-like behaviors of mice in each group were tested with the sucrose preference test, forced swimming test, tail suspension test, and open field test. Meanwhile, the three key neuroendocrine hormones (corticotropin releasing hormone, adrenocorticotropic hormone and corticosterone) in HPA axis pathway, and the level of the emotion-related monoamine neurotransmitters (5-hydroxytryptamine and norepinephrine) were measured using enzyme-linked immunosorbent assay. Furthermore, total mercury in the hypothalamus and hippocampus were determined using an automatic, direct mercury analyzer. RESULTS: Zuotai or imipramine significantly increased the body weight and the sucrose preference ratio in sucrose preference test, and dramatically improved motor activity in forced swimming test, tail suspension test, and open field test in CUMS mice. Zuotai or imipramine remarkably decreased levels of corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone in the HPA axis, and increased levels of 5-hydroxytryptamine and norepinephrine in the serum in CUMS mice. However, a small amount of mercury was deposited in the hypothalamus and hippocampus in Zuotai-treated mice, which may pose a potential risk to the central nervous system. CONCLUSION: Zuotai has a strong ability to ameliorate depressive-like behaviors in CUMS-treated mice through inhibition of the HPA axis and upregulation of monoamine neurotransmitters. These findings provide new insight into the pharmacological effect of Zuotai on depression.
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Prenatal stress-induced HPA hyperreactivity coexists with alterations in HDAC/DNMT activity.
“Animal studies demonstrate that prenatal stress-induced HPA hyperreactivity coexists with alterations in HDAC/DNMT activity”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Zhao et al., 2018
The Introduction (page unavailable) says chronic adverse stress can cause HPA-axis hyperactivity. It does not identify that stress as prenatal, and the passages retrieved from our copy do not address HDAC or DNMT activity or its coexistence with HPA hyperreactivity. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThere is emerging evidence for the use of modular, trans-diagnostic psychological treatments (compared with 'disorder' specific treatments).
“and emerging evidence for the use of modular, trans-diagnostic psychological treatments (compared with 'disorder' specific treatments). 692”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [692]
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- Authors
- Zhao, J., Niu, C., Wang, J., Yang, H., Du, Y., Wei, L., & Li, C.
- Affiliations
- Chinese Academy of Sciences (CN)
- University of Chinese Academy of Sciences (CN)
- Corresponding author
- Wei, Lixin
- Li, Cen
- Venue
- Neuropsychiatric Disease and Treatment
- Publisher
- Informa UK Limited
- Published
- 2018-01
- Volume
- Volume 14
- Pages
- 129-141
- ISSN
- 1176-6328 (ISSN-L)
- 1178-2021
- PMC
- PMC5757979
- OpenAlex
- W2782432378
- Cited by
- 49
- References
- 49
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 8 · 2021: 5 · 2020: 6 · 2019: 9 · 2018: 1
- FWCI
- 7.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neuropsychiatric Disease and Treatment (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- National Natural Science Foundation of China (81374063, 2017-ZJ-Y08)
- Chinese Academy of Sciences (Y529021211, 2017-ZJ-Y08, 81374063, 2016-ZJ-919Q)
- National Institutes of Health
- National Institute of Environmental Health Sciences
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Medicinal Plants and Bioactive Compounds
- Keywords
- Tibetan medicine, metacinnabar, chronic unpredictable mild stress, depression, depression-like behavior, hypothalamic-pituitary-adrenal axis, corticotropin-releasing factor, ACTH, corticosterone, serotonin, norepinephrine, mercury accumulation, hypothalamus, hippocampus, imipramine
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