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

Jing Zhao,1,2 Cuiying Niu,1–3 Jianv Wang,1,3 Hongxia Yang,1,2 Yuzhi Du,1,2 Lixin Wei,1,2 Cen Li1,2 1Pharmacology and Safety Evaluation Key Laboratory of Tibetan Medicine in Qinghai Province, Northwest Institute of Plateau Biology, 2Key Laboratory of Tibetan Medicine Research, Chinese Acad...

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Autores principales: Zhao J, Niu C, Wang J, Yang H, Du Y, Wei L, Li C
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Publicado: Dove Medical Press 2018
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spelling oai:doaj.org-article:e3327797c81b4cf1a0585f9e072d032b2021-12-02T07:45:39ZThe depressive-like behaviors of chronic unpredictable mild stress-treated mice ameliorated by Tibetan medicine Zuotai: involvement in the hypothalamic–pituitary–adrenal (HPA) axis pathway1178-2021https://doaj.org/article/e3327797c81b4cf1a0585f9e072d032b2018-01-01T00:00:00Zhttps://www.dovepress.com/the-depressive-like-behaviors-of-chronic-unpredictable-mild-stress-tre-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Jing Zhao,1,2 Cuiying Niu,1–3 Jianv Wang,1,3 Hongxia Yang,1,2 Yuzhi Du,1,2 Lixin Wei,1,2 Cen Li1,2 1Pharmacology and Safety Evaluation Key Laboratory of Tibetan Medicine in Qinghai Province, Northwest Institute of Plateau Biology, 2Key Laboratory of Tibetan Medicine Research, Chinese Academy of Sciences, Xining, Qinghai, 3University of Chinese Academy of Sciences, Beijing, People’s Republic of China 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 axisZhao JNiu CWang JYang HDu YWei LLi CDove Medical PressarticleTibetan medicineZuotaiHgSDepressionChronic unpredictable mild stress (CUMS)HPA axisNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 14, Pp 129-141 (2018)
institution DOAJ
collection DOAJ
language EN
topic Tibetan medicine
Zuotai
HgS
Depression
Chronic unpredictable mild stress (CUMS)
HPA axis
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
spellingShingle Tibetan medicine
Zuotai
HgS
Depression
Chronic unpredictable mild stress (CUMS)
HPA axis
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Zhao J
Niu C
Wang J
Yang H
Du Y
Wei L
Li C
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
description Jing Zhao,1,2 Cuiying Niu,1–3 Jianv Wang,1,3 Hongxia Yang,1,2 Yuzhi Du,1,2 Lixin Wei,1,2 Cen Li1,2 1Pharmacology and Safety Evaluation Key Laboratory of Tibetan Medicine in Qinghai Province, Northwest Institute of Plateau Biology, 2Key Laboratory of Tibetan Medicine Research, Chinese Academy of Sciences, Xining, Qinghai, 3University of Chinese Academy of Sciences, Beijing, People’s Republic of China 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
format article
author Zhao J
Niu C
Wang J
Yang H
Du Y
Wei L
Li C
author_facet Zhao J
Niu C
Wang J
Yang H
Du Y
Wei L
Li C
author_sort Zhao J
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort depressive-like behaviors of chronic unpredictable mild stress-treated mice ameliorated by tibetan medicine zuotai: involvement in the hypothalamic–pituitary–adrenal (hpa) axis pathway
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/e3327797c81b4cf1a0585f9e072d032b
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