Abstract
Baicalin, the main active flavonoid constituent of Scutellaria baicalensis Georgi, has been reported to exert antidepressant effects. Hypothalamic-pituitary-adrenal (HPA) axis plays important roles in depression. However, antidepressant effect and mechanism of baicalin on HPA axis in hypothalamus are still unknown. In present study, we find baicalin significantly attenuates the increase of immobility time in tail suspension and forced swimming, improves the decrease of spending time in open arms, and restores the aberrant negative feedback of HPA axis in chronic corticosterone (CORT)-induced depressed mice. Moreover, proteomics finds 370 differentially expressed proteins after baicalin treatment, including 114 up-regulation and 256 down-regulation in hypothalamus. Systems biology analysis indicates the functions of differentially expressed proteins focus on phosphoserine binding and phosphorylation, especially participate in GR signaling pathway. Finally, our findings demonstrate that baicalin normalizes hypothalamic GR nuclear translocation via reducing GR phosphorylation to remodel negative feedback of HPA axis in CORT-induced mice.
Highlights
Depression is the kind of affective disorder, which seriously threatens human health and brings heavy social burdens (McEwen et al, 2015)
The results showed that the immobility time in tail suspension test and forced swimming test was increased by chronic CORT (P = 0.024, P = 0.002), while baicalin and fluoxetine treatment could recover this enhancement (Figures 2A,B)
These data indicate that baicalin has definite antidepressant effect in CORT-induced mice
Summary
Depression is the kind of affective disorder, which seriously threatens human health and brings heavy social burdens (McEwen et al, 2015). Most antidepressant drugs are developed according to the phenomenon which deficient monoamine neurotransmitters are discovered in depressive patients (Boku et al, 2018). Patients are usually unsatisfied with the therapeutic effects due to the delayed actions and side effects (Duman and Aghajanian, 2012). Many studies show that the abnormal HPA axis participates in depression (Anacker et al, 2011b). Hypothalamus has important modulatory function in brain, which controls the activity of hypothalamicpituitary-adrenal (HPA) axis and responds to the stress (Myers et al, 2014). The role of hypothalamus in abnormal HPA axis and the molecular mechanisms of antidepressant drug in hypothalamus have not been definitely illuminated. Proteomics is new-style development of biological systems, which possessed the powerful capacity to analyze proteins by high throughput
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