Study On The BDNF/MEK-ERK/CREB Molecular Mechanism Antidepressant Effects Of Xiaoyao Powder

Objective:To study the antidepressant effects and BDNF/MEK-ERK/CREB signal pathway mechanism of classical prescription Xiaoyao Powder,which reveals the function of BDNF’s signal pathway in depressed liver syndromes and therapy methods of Shugan Jieyu.Methods:(1)Mice were subjected to different mild unpredictable stressors and single cage feeding for6weeks to establish the animal model of depression.The decoction of Xiaoyao Powder(30,20,10g/kg)was administrated two weeks after stress procedure, and the weight, locomotor activity and sweet water consumption of mice were observed at diferent time points. Morris maze test was used to evaluate the spatial learning and memory ability of CUMS model mice.(2) The level of monoamine neural transmitters in brain and BDNF in serum of CUMS model mice affected by Xiaoyao Powder was detected by ELISA assays.(3) The level of MDA and SOD in liver of CUMS model mice affected by Xiaoyao Powder was detected by assays.(4)BDNF、CREB mRNA expressions in hippocampus and cortical area were assayed by real-time fluorescent quantitative PCR.(5)The expressions of ERK,p-ERK (phosphorylation ERK),p-RSK,p-CREB protein was assayed by Western blot technique.(6) The tail suspension test, forced swimming test combined with administrating by the blocking agent of MEK(PD184161) were adopted in mice, and the antidepressant effects of Xiaoyao Powder were observed.Results:(1)30,20,10g/kg of Xiaoyao Powder obviously increased weight and locomotor activity of CUMS model mice,while30,20g/kg of Xiaoyao Powder increased the sweet water consumption of CUMS model mice.Xiaoyao Powder30g/kg also elevated the spatial learning and memory ability of CUMS model mice.(2)Xiaoyao Powder30g/kg could increase the concentration of5-HT,DA,NE in hippocampus area and NE in cortical area of CUMS model mice,while20g/kg Xiaoyao Powder could increase the concentration of5-HT,DA in hippocampus area and DA in cortical area.(3)30,20g/kg of Xiaoyao Powder obviously decreased the concentration of MDA in liver and showed the trend of increasing the concentration of SOD of CUMS model mice (4) Xiaoyao Powder30g/kg significantly up-regulated CREB、BDNF mRNA expressions in hippocampus area and BDNF mRNA expression in cortical area of CUMS model mice.(5)Xiaoyao Powder30g/kg increased the expressions of p-RSK in hippocampus area and p-CREB in cortical area of CUMS model mice,while it also has significant tendency to increase the expression of p-ERK protein in hippocampus area.(6)Xiaoyao Powder30g/kg has significant tendency to increase the concentration of BDNF in serum of CUMS model mice.(7)Administrated for7days, Xiaoyao Powder30g/kg significantly shortened the immobility time in the tail suspension test and forced swimming test combined with administrating by PD184161in mice.Conclusions:(1)Xiaoyao Powder could improve weight, locomotor activity and sweet water consumption abnormalities of CUMS model mice, Xiaoyao Powder could also evaluate the spatial learning and memory ability of CUMS model mice.(2) Xiaoyao Powder obviously decreased the concentration of MDA in liver of CUMS model mice and showed the trend of increasing the concentration of SOD,which could raise liver’s antioxidant stess ability of CUMS model mice.(3)Xiaoyao Powder up-regulated BDNF,CREB mRNA expressions and expressions of p-RSK,p-CREB protein in brain of CUMS model mice,it also againsted the function of PD184161(MEK blocker).In conclusion,Xiaoyao Powder could activate BDNF/MEK-ERK/CREB signaling pathway in brain of CUMS model mice to realize its antidepressant effects.