Objective:To investigate the antidepressant-like effects of Chaihu Shugan Powder(CSP,柴胡疏肝散)and to explore its underlying mechanisms.Methods:Thirty-two Sprague-Dawley rats were randomly divided into control(CON),c...Objective:To investigate the antidepressant-like effects of Chaihu Shugan Powder(CSP,柴胡疏肝散)and to explore its underlying mechanisms.Methods:Thirty-two Sprague-Dawley rats were randomly divided into control(CON),chronic unpredictable mild stress(CUMS),fluoxetine(FLU),and CSP groups,8 rats in each group.All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model.The open field test(OFT),forced swimming test(FST),and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP.Terminal deoxynucleotidyl transferase(Td T)d UTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues.The m RNA and protein levels of glucose-regulated protein(GRP)78,spliced X-box-binding protein(XBP)-1,CCAAT/enhancerbinding protein homologous protein(CHOP),caspase-12,and c-Jun N-terminal kinase(JNK)in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis,respectively.Results:Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats,as revealed by enhanced time and distance in the center of the OFT(P<0.05),an increased preference for sucrose,and longer swimming time and shorter immobility time during the FST(all P<0.05).In addition,CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons(P<0.05).The m RNA and protein expression levels of GRP78,spliced XBP-1,and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins(all P<0.05),whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats.Conclusion:CSP can improve depression-like behavior in rats exposed to CUMS,possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.展开更多
基金Supported by National Natural Science Foundation of China(No.81574038)Shenzhen Science and Technology Program(No.JCYJ20180508152437368)Sanming Project of Medicine in Shenzhen,China(No.SZSM201612049)。
文摘Objective:To investigate the antidepressant-like effects of Chaihu Shugan Powder(CSP,柴胡疏肝散)and to explore its underlying mechanisms.Methods:Thirty-two Sprague-Dawley rats were randomly divided into control(CON),chronic unpredictable mild stress(CUMS),fluoxetine(FLU),and CSP groups,8 rats in each group.All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model.The open field test(OFT),forced swimming test(FST),and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP.Terminal deoxynucleotidyl transferase(Td T)d UTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues.The m RNA and protein levels of glucose-regulated protein(GRP)78,spliced X-box-binding protein(XBP)-1,CCAAT/enhancerbinding protein homologous protein(CHOP),caspase-12,and c-Jun N-terminal kinase(JNK)in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis,respectively.Results:Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats,as revealed by enhanced time and distance in the center of the OFT(P<0.05),an increased preference for sucrose,and longer swimming time and shorter immobility time during the FST(all P<0.05).In addition,CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons(P<0.05).The m RNA and protein expression levels of GRP78,spliced XBP-1,and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins(all P<0.05),whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats.Conclusion:CSP can improve depression-like behavior in rats exposed to CUMS,possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.
