Timosaponin B-III exhibits antidepressive activity in a mouse model of postpartum depression by the regulation of inflammatory cytokines, BNDF signaling and synaptic plasticity.

The aim of this study was to investigate the antidepressive effects of timosaponin B-III (TB-III) and the underlying mechanism. A postpartum depression (PPD) mouse model was established by the administration of dexamethasone sodium phosphate during pregnancy. Mice with PPD were assigned to the following groups: Model, fluoxetine and high, medium and low doses of TB-III. Post-parturient mice without PPD served as a normal control group. To examine the effect of TB-III, mice were treated with TB-III, then forced swimming tests (FSTs) and tail suspension tests (TSTs) were performed to evaluate depression. Serum and hippocampal cytokines, namely tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10, were quantified using ELISAs and protein levels of hippocampal brain-derived neurotrophic factor (BDNF), glucagon synthase kinase (GSK)-3β, glutamate receptor subunit 1 (GluR1), postsynaptic density protein 95 (PSD95) and synapsin I were quantified using western blot analysis. Compared with those in the control group, immobility time in the FST and TST, serum and hippocampal TNF-α, IL-1β and IL-6 levels and hippocampal IL-10 levels were increased significantly in the model group (P<0.01). Serum IL-10 levels and hippocampal levels of BDNF, GSK-3β, GluR1, PSD95 and synapsin I decreased significantly in the model group compared with the control group (P<0.01). Fluoxetine or TB-III (10, 20 or 40 mg/kg) treatment significantly decreased immobility times in the FST and TST (P<0.01) and significantly reversed the aforementioned alterations in cytokine and protein levels (P<0.01). Thus, TB-III exhibited a protective effect against depression in PPD and such effects may have been mediated via the regulation of inflammatory cytokines, the BNDF signaling pathway and synaptic plasticity-related proteins.