ObjectiveTo decipher the mechanism of Wenxiao
powder in alleviating
corticosterone-induced
depression-like
behaviors in
mice. MethodMale
ICR mice were randomized into normal, model,
paroxetine (20 mg·kg-1), and low- and high-
dose (3.27, 6.54 g·kg-1, respectively) Wenxiao
powder groups. The
mice in normal and model groups received equal volume of saline. Other groups except the normal group were injected with
corticosterone subcutaneously 0.5 h after gavage to induce
depression.
Mice were tested for
depression-like
behaviors after
drug administration.
Enzyme-linked immunosorbent assay (
ELISA) was performed to
measure the
corticosterone content in the
serum. Nissl
staining was performed to observe the damage of hippocampal
neurons.
Immunofluorescence staining was employed to observe the expression of double cortin (DCX) in the
dentate gyrus (DG) of the
hippocampus.
Western blot was employed to determine the expression of
proteins in the
brain-derived neurotrophic factor (
BDNF)/
tyrosine kinase receptor B (TrkB)/
extracellular signal-regulated kinase (ERK)/cAMP-
response element-
binding protein (CREB) pathway in the
hippocampus. ResultCompared with the normal group, the model group showed decreased
sucrose preference rate, increased immobility
time in the
tail suspension test (P<0.01), and reduced
residence time in the central area of the open field and the total
movement distance (P<0.05, P<0.01). In addition, the modeling elevated the
corticosterone level in the
serum (P<0.01), decreased the volume and intensified the nuclear
staining of hippocampal
neurons in the DG area, reduced the expression of DCX in the DG area, and down-regulated the
protein levels of
BDNF, phosphorylated (p)-TrkB, p-ERK, and p-CREB in the
hippocampus (P<0.05, P<0.01). Compared with the model group, low-
dose Wenxiao
powder improved the
mouse behavivors in the
sucrose preference, open field, and
tail suspension tests (P<0.05, P<0.01), and high-
dose Wenxiao
powder improved the
behaviors in the
sucrose preference and
open field tests (P<0.05, P<0.01). In addition, Wenxiao
powder lowered the
serum corticosterone level (P<0.01) and recovered the structure and morphology of
neurons with obvious nuclei and presence of
Nissl bodies in the DG area of the
hippocampus. Moreover, Wenxiao
powder at both doses promoted the expression of DCX in the DG area, and high-
dose Wenxiao
powder up-regulated the
protein levels of
BDNF, p-TrkB, p-ERK, and p-CREB in the
hippocampus (P<0.05, P<0.01). ConclusionWenxiao
powder can alleviate
corticosterone-induced
depression-like
behaviors and promote
neurogenesis in
mice possibly by activating the
BDNF/TrkB/ERK/CREB signaling pathway.