Researches On The Antidepressant Effect And Mechanisms Of Total Timosaponin And Magnolol In Depression Rat Modal

Objective:To study the effects and machanisms of the total timosaponin and magnolol for the depressive behaviors in chronic stress depression rat modal.Methods:12-14months old SD male rats(weight at180-220g) were choosed, and rats were subjected to a variety of chronic and unpredictable stressors plus separation for30days except the control group. Rats behaviors, included body weight, open-field, food intake, surcrose solution comsumption, forced swimming and suspending tail test were measured to evaluate the efficiency of the modal, and they were randomly divided into control group, stress group, Total Timosaponin group, magnolol group and Fluoxetine group, with30days for chronic and unpredictable stressors while oral adminstraion. Then the neurotransmitters level in crerbral cortex and CORT level in serum were investigated respectively by HPLC-FLD and ELISA, the thickness of adrenal gland and structure changes of hippocampus were examined by HE stain, rats hippocampal neurons were observed by electron microscope, the changes of GR and BDNF protein expression were observed with immunohistochemical method then the amount of positive cells were calculated; mRNA levels of GR and BDNF were analysised by PT-PCR, for studying the differences before and after drugs administration.Results:Comparing for the control group, neurotransmitters decreased in rats brain; serum corticosterone concentration increased; the thickness of Adrenal cortex increased; pathological structures appeared of the hippocampal neurons; the amount of positive cells decreased for GR and BDNF protein expression; GR and BDNF mRNA levels decreased for the depression modal rats. Total Timosaponin and Magnolol could decrease the serum coricosterone concentration; Abnormal hyperplasia of the adrenal cortex and impaired hippocampal neurons were improved; Protein expression and mRNA level from hippocampus with immunohistochemical and PT-PCR methods were improved. The results implicated that Total Timosaponin and Magnolol had some certain intervention treatment effects for the depressive rats.Conclusion:Drugs administration groups can be difference from the stress group. It was concluded that Total Timosaponin and Magnolol can significance changed the rats depression behaviors and Biochemical Characters induced by chronic stressors and have antidepression effects. The possible antidepressant machanisms might be mediated by improving the monoamine neurotransmitters level, inhibiting the hyperactivity of the HPA axis and upregualating the mRNA expression of GR and BDNF.