ABSTRACT
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.
ABSTRACT
Objective To investigate the combining anticancer effect of tamoxifen(TAM) and ?-interferon on breast cancer cells in vitro and its mechanism.Methods MCF-7 ER-positive breast cancer cell lines were treated with tamoxifen alone,or in combination with ?-interferon and/or estrogen in vitro.Cell proliferation was evaluated by MTT assay;FCM was used to determine the distribution of cell cycle,cell apoptosis and protein expression of Bcl-2,Bax,Fas,FasL,Caspase-8,and the activity of Caspase-3.Results TAM inhibited the proliferation of ER-postive breast cancer cells with cell cycle arrest in G0/G1 phase and with induction of apoptosis,and the proliferation-promoting effect of estrogen on MCF-7 was blocked by TAM.Anticancer effect of TAM was enhanced when cells were pretreated with ?-interferon for 24 hours.Bcl-2 protein expression was down-regulated and Caspase-8 was up-regulated by TAM and/or ?-interferon,but these drugs did not affect Bax,Fas,FasL protein expression and the activity of Caspase-3.Conclusions TAM has anticancer effect by inhibiting proliferation and inducing apoptosis in ER-positive breast cancer cells in vitro,and ?-interferon can enhance anticancer effect of TAM on breast cancer cells.The mechanism of these effects may be related with the down-regulation of Bcl-2 expression and up-regulation of Caspase-8 by TAM and ?-interferon.