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

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.

Optimization of food deprivation and sucrose preference test in SD rat model undergoing chronic unpredictable mild stress

“…Depression is a chronic heterogeneous mental disease associated with high prevalence, recurrence, and mortality, with serious implications for human physical and mental health 1‐4 . The World Health Organization has predicted that by 2020 it will become the second leading cause of disability worldwide and by 2030 major depressive disorders (MDDs) will represent the main cost in healthcare spending 5,6 . Although progress has been made in the research and treatment of depression in recent years, the exact pathogenesis of this disease is still not clear, and experimental results from animal models are not in good agreement with those of clinical trials 7 .…”

Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/β-catenin pathway in rats

“… 19 Moreover, depression-like effects in rats induced by chronic stress or glucocorticoid administration have been reported to be related to reduced hippocampal BDNF levels. 20 , 21 Furthermore, some antidepressants are reported to achieve their efficacy by increasing hippocampal BDNF expression. 22 , 23 Although the underlying mechanisms remain unknown, it has been reported that BDNF appears to be a direct target of Wnt signaling.…”

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“…The antidepressantlike the action of bacon aside I (BS I) was investigated using a mouse model of behavioral deficits induced by chronic unpredictable mild stress (CUMS) for 5 weeks to induce depression. The oral administration of BS ameliorated CUMSinduced depression-like behaviors in mice 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 CUMSexposed mice was restored by BS-I treatment 36 .…”