Effects of β-asarone on expression of endoplasmic reticulum stress regulators GRP78, ATF6, XBP1 in hippocampus of depressive rats

CAI Zhen-zhen; JIN Ming; YANG Pan-pan; LI Cheng-chong; DONG Hai-ying; ZHAO A-meng; ZHANG Xiao-jie

Abstract：Objective:In order to observe the effects of β-asarone on the expressions of the endoplasmic reticulum stress related factors of rats with chronic unpredictable mild stress (CUMS).Methods:SD rats were randomly divided into 5 groups:control group,model group,fluoxetine group,β-asarone low-dose group,β-asarone high-dose group.The rats were established by CUMS,and then on the 8th day after the model establishment,rats in fluoxetine group and β-asarone group were treated with fluoxetine(10 mg·kg-1) orβ-asarone(25,50 mg· kg-1)once daily by intragastric administration.The experiments of sucrose consumption (SPT) and open field test were carried out to assess the CUMS model and rat ethological changes on the 0th and 29th day.the apoptosis of hippocampal neuronal cells was investigated by flow cytometry test.And the protein expressions of GRP78,ATF6,XBP1 were detected by Western Blot.Results:The results of the SPT and open field test showed no significant differences between each group (P ＞ 0.05).After CUMS for 28 days,the scores of horizontal motion,vertical motion and sucrose consumption in model group were reduced obviously compared with control group (P ＜ 0.05),which inβ-asarone low-dose group,β-asarone high-dose group,fluoxetine group were increased compared with model group (P ＜ 0.05).The cell apoptosis rate was increased obviously in the model group compared with that in control group by flow cytometry detection (P ＜ 0.05),but the treatments of β-asarone and fluoxetine repressed the cell apoptosis significantly (P ＜ 0.05).By Western Blot detection,the results showed that the ATF6 protein expressions were significantly increased in the model group compared with control group (P ＜ 0.05),but no significant differences exhibited in the expressions of the GRP78 and XBP1 (P ＞ 0.05);β-asarone group and fluoxetine group compared with the model group,in which the protein expressions of the ATF6 were decreased(P ＜0.05),meanwhile the GRP78 and XBP1 protein levels were significantly increased (P ＜ 0.05).Conclusion:β-asarone could significantly reduce the apoptosis of hippocampal neuronal cells and relieve the stress state of the endoplasmic reticulumand and improve depression-like behavior in CUMS rats.