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.