AUTHOR=Li Cen , Niu Cuiying , Bi Hongtao , Zhao Jing , Ivan Alvarez Jorge , Yuan Farong , Gai Xiangyun , Wei Lixin , Du Yuzhi , Qiao Yajun , Kebir Hania , Xiao Yuancan , Yang Hongxia 

TITLE=Tibetan mineral-herbal medicine Zuotai alleviates the depressive-like behaviors in chronic restraint-stressed mice while regulating stress hormone, inflammation and monoamine

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1098378

DOI=10.3389/fphar.2023.1098378

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold><italic>Zuotai</italic> is an ancient mineral-herbal mixture containing β-HgS in Tibetan medicine. It is used to treat nervous system diseases, similar to Chinese medicine cinnabar and Indian Ayurveda medicine <italic>Rasasindura</italic>. However, one of the key problems faced by <italic>Zuotai</italic> is that its indications are ambiguous. Our previous study found that <italic>Zuotai</italic> exhibited the activity of ameliorating depressive-like behaviors in a chronic mild stress model. However, due to the inherent limitations of animal models in simulating human disease, clear results often require more than one model for confirmation.</p><p><bold>Methods:</bold> Therefore, another depression model, chronic restraint stressed (CRS) mice, was used to validate the antidepression effect of <italic>Zuotai</italic>. Prophylactic treatment was conducted for 21 consecutive days while mice were subjected to chronic restraint stress.</p><p><bold>Results:</bold> It was observed that <italic>Zuotai</italic> and β-HgS alleviated anhedonia, behavioral despair, stereotype behavior, and reduced exploratory and spontaneous movement in CRS mice. <italic>Zuotai</italic> and β-HgS also reversed the increases of stress hormone corticosterone (Cort) in serum and pro-inflammatory cytokines in serum and brain, and increased the serotonin in cortex in CRS mice, with positive dose-effect relationship. The number of Ki67-positive cells in the dentate gyrus and the level of brain-derived neurotrophic factor (BDNF) in the hippocampus were slightly elevated in CRS mice treated with <italic>Zuotai</italic>; however, there was no statistically significant difference. Although <italic>Zuotai</italic> increased the total Hg concentration in main organs, the levels remained below those needed to result in observed adverse effect, at least for kidney and liver; and <italic>Zuotai</italic> showed no observed adverse effect on the brain histopathology, the cell proliferation in dentate gyrus, as well as the hippocampal and cortical organ coefficients.</p><p><bold>Conclusion:</bold><italic>Zuotai</italic> exhibited the alleviation of depressive-like behaviors in CRS mice, accompanying with ameliorating stress hormone, peripherical and cerebral inflammation, and monoamine neurotransmitter.</p>