Antidepressant Effect Of Traditional Chinese Medicine Compound Zhijiang Jieyu Decoction And Its Mechanism

Objective:To explore the hippocampus (HP) and prefrontal cortex (PFC) neuronal damage and basic fibroblast growth factor (bFGF) changes in multivariate chronic unpredictable stressor-induced depression model mice. To explore the anti-depression role and its mechanism of the Zhijujieyu-tang, a Chinese herbal compound, that from behavior, pathomorphology and molecular biology.Methods:Healthy Kunming mice were randomly divided into control group, model group, positive control (fluoxetine) group, Chinese herbal compound group (including low, medium and high concentration of Zhijujieyu-tang group). Depression model mice were established by using multi chronic unpredictable stressors. Distilled water given to the control group and the model group mice, and fluoxetine given to the positive control group, and different concentration of Zhijujieyu-tang given to the each Chinese herbal compound group by intragastric injection (ig) in every day, respectively.We measure the body weight of mice changes in the stress processes in phases. The change of mice behavior and emotion were determined using open-field and tail suspension test. The spatial learning-memory ability were detected by Morris water maze. Morphological structure changes of neurons in HP and PFC were detected by HE dye. Immunohistochemical methods were used to measure bFGF expression in HP and PFC. The changes of LDH and GSH-PX activity were examined too.All data were expressed by the mean±standard error (Mean±SE.). Using analysis of variance (ANOVA) and N-K or t test was used for statistical analysis of data.Results:Model group weight growth rate has slowed down significantly; positive control and medium concentration group of Zhijujieyu-tang group were significantly higher than model group, low and high concentration group growth small, in the stress process.Behavioral results show that the medium concentration group of Zhijujieyu-tang group and the positive control group all can improve the depressive behavior in mice, including mice exploring behavior in new different environment, the level of tension; depression and the degree of despair in the tail suspension test; the spatial learning and memory in Morris water maze, with a significant difference compared with the model group (P<0.05, P<0.01).Enzyme activity test results showed that Chinese traditional herb prescription group and the positive control group can improve the GSH-PX activity, reduce LDH activity, reducing neuronal damage, and have a significant difference (P<0.05) with the model group. Morphological analysis of the HP and PFC neurons:positive control group and both medium and high concentration group of Zhijujieyu-tang hippocampus neurons neatly close level, the nucleus is located in the cell center with dark blue, the PFC neuronal morphology regular clear homogeneous staining. The model group HP and PFC neurons appear karyopyknosis, the number reduced, cells were loose irregular, apoptosis occurs, and the cells were stained with shallow, uneven coloring, even can see some deformed cells.Immunohistochemical analysis of bFGF:Compare with the model group, Chinese traditional herb prescription group and positive control group can significantly improved the expression of bFGF in HP and PFC (P<0.05, P<0.01). The number of bFGF positive cells were remarkably increased, and the average target gray value were markedly decreased.Conclusions:Established mouse model of depression by using Long-term chronic stress multifactorial, we can see hippocampal and forebrain neuronal damage in their brain. Zhijujieyu-tang can improve and recover neuronal damage maybe by increasing bFGF expression and GSH-PX activity.Zhijujieyu-tang showed some antidepressant effect by improving depression performance and spatial learning and memory decline on the mice model of depression.Zhijujieyu-tang can increase bFGF expression and GSH-PX activity in HP and PFC of depressive model mice brain, reduce the damage of neuron. This may be the antidepressant mechanism of Zhijujieyu-tang.