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Antidepressant-like Effect of Bacopaside I in Mice Exposed to Chronic Unpredictable Mild Stress by Modulating the Hypothalamic–Pituitary–Adrenal Axis Function and Activating BDNF Signaling Pathway

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Abstract

Preliminary studies conducted in our laboratory have confirmed that Bacopaside I (BS-I), a saponin compound isolated from Bacopa monnieri, displayed antidepressant-like activity in the mouse behavioral despair model. The present investigation aimed to verify the antidepressant-like action of BS-I using a mouse model of behavioral deficits induced by chronic unpredictable mild stress (CUMS) and further probe its underlying mechanism of action. Mice were exposed to CUMS for a period of 5 consecutive weeks to induce depression-like behavior. Then, oral gavage administrations with vehicle (model group), fluoxetine (12 mg/kg, positive group) or BS-I (5, 15, 45 mg/kg, treated group) once daily were started during the last two weeks of CUMS procedure. The results showed that BS-I significantly ameliorated CUMS-induced depression-like behaviors in mice, as characterized by an elevated sucrose consumption in the sucrose preference test and reduced immobility time without affecting spontaneous locomotor activity in the forced swimming test, tail suspension test and open field test. It was also found that BS-I treatment reversed the increased level of plasma corticosterone and decreased mRNA and protein expressions of glucocorticoid receptor induced by CUMS exposure, indicating that hypothalamic–pituitary–adrenal (HPA) axis hyperactivity of CUMS-exposed mice was restored by BS-I treatment. Furthermore, chronic administration of BS-I elevated expression levels of brain-derived neurotrophic factor (BDNF) (mRNA and protein) and activated the phosphorylation of extracellular signal-regulated kinase and cAMP response element-binding protein in the hippocampus and prefrontal cortex in mice subjected to CUMS procedure. Taken together, these results indicated that BS-I exhibited an obvious antidepressant-like effect in mouse model of CUMS-induced depression that was mediated, at least in part, by modulating HPA hyperactivity and activating BDNF signaling pathway.

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Abbreviations

BDNF:

Brain-derived neurotrophic factor

BS-I:

Bacopaside I

CUMS:

Chronic unpredictable mild stress

FST:

Forced swimming test

GR:

Glucocorticoid receptor

HPA:

Hypothalamic–pituitary–adrenal

MR:

Mineralocorticoid receptor

OFT:

Open field test

Pcreb:

Phosphorylated cAMP response element-binding protein

pERK1/2:

Phosphorylated extracellular signal-regulated kinase ½

SPT:

Sucrose preference test

TST:

Tail suspension test

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Acknowledgements

This work was supported by the National Major Project of China (2011ZX09307-002-03), the National Natural Science Foundation of China (81230090, 81520108030, 81573318, 81373301 and 1302658), the Scientific Foundation of Shanghai China (13401900103, 13401900101 and 12401900801).

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    Authors and Affiliations

    1. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China

      Xianpeng Zu, Wencai Li, Haisheng Xie, Zhang Lin, Niao Yang, Xinru Liu & Weidong Zhang

    2. Institute of Interdisciplinary Complex Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

      Weidong Zhang

    3. Institute of Immunology, Second Military Medical University, Shanghai, 200433, China

      Mingjian Zhang

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    Xianpeng Zu and Mingjian Zhang have contributed equally to this work.

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    Zu, X., Zhang, M., Li, W. et al. Antidepressant-like Effect of Bacopaside I in Mice Exposed to Chronic Unpredictable Mild Stress by Modulating the Hypothalamic–Pituitary–Adrenal Axis Function and Activating BDNF Signaling Pathway. Neurochem Res 42, 3233–3244 (2017). https://doi.org/10.1007/s11064-017-2360-3

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