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

Abstract

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.

Keywords:

• Tibetan medicine
• Zuotai
• HgS
• depression
• chronic unpredictable mild stress
• CUMS
• HPA axis

Acknowledgments

The Science Foundation for Young Scholars of Qinghai Province (2016-ZJ-919Q), “The Dawn of West China” 2014 Talent Training Program of Chinese Academy of Sciences (Y529021211), the National Natural Science Foundation of China (81374063), and Development Program of Key Laboratory in Qinghai Province (2017-ZJ-Y08) supported this study. The authors declare that the sponsors did not play any role in the study design. The authors thank Dr Sheng Song (PhD) and Professor Jie Liu (PhD), National Institute of Environmental Health Sciences (NIEHS), NIH for the English language copyediting of this manuscript.

Disclosure

The authors report no conflicts of interest in this work.