Antidepressive Effects And Mechanisms Of Chinese Traditional Medicine "SXY-006"

Depression is a common and debilitating thymogenic mental disorder in clinic, characterized by marked and long-lasting depressed mood. Previous studies show that the pathogenesis of depression correlates with the abnormity of neuroendocrine and immune system and the expression of certain genes. Depression is primarily treated by drug therapy. The clinically used medications include selective serotonin reuptake inhibitors(SSRIs, e.g. fluoxetine),TCAs (e.g. amitripramine) and monoamine oxidase inhibitor (MAOIs, e.g. maclobemide). All of the drugs are effective in treating some subpopulation of depression patients, however, they also have certain side effects or physical dependence, and under some conditions they even aggravate the process. Therefore, it is necessary to find new drug, which has good antidepressive effect and less adverse reaction.The thesis consists of two parts: preclinical evaluation of the antidepressant efficacy of new TCM SXY-006 and the investigation of its mechanism. By using several behavioral and morphological experiment for antidepressants, the goal of this series of studies is to evaluate the antidepressant effects of SXY-006 and elucidate its mechanisms, thus to provide convinced preclinical information for NDA (New Drug Application). Part I Antidepressant effects of traditional Chinese medicine"SXY-006"Objective: To evaluate the antidepressant effects of traditional Chinese medicine"SXY-006"Methods: The effect of SXY-006 on immobility time was investigated by the tail suspension test and force swimming test of mice or rats after single and multiple administrations. The effect of SXY-006 on horizontal and vertical score was studied through the open-field test after the establishment of chronic unpredictable mild stress (CUMS) model of rats.Results: Moderate (100 mg/kg) and high (300 mg/kg) doses of SXY-006 can obviously decrease the immobility time in the tail suspension and forced swimming tests of mice (p<0.01). All of SXY-006 in different doses can markedly reduce the immobility time in forced swimming tests of rats after both the single and multiple administrations of the medicine (p<0.05), and raise the horizontal score (p<0.05) and vertical score (p<0.01) in chronic unpredictable mildstress model of rats.Conclusion: The new TCM SXY-006"SXY-006"has good antidepressant effect. Partâ…¡Antidepressant mechanisms of traditional Chinese medicine"SXY-006"Objective: To investigate antidepressant mechanisms of traditional Chinese medicine"SXY-006"Methods: The effect of SXY-006 on the times of 5-HTP induced head-twitches and reserpine induced eyes shutting and independence movement were observed. HE stain was applied to observe the morphological change of hippocampal neurons. The expression of the 5-HT2 and c-fos were analyzed by immunohistochemistry experiment.Results: Different doses of SXY-006 can markedly increase the times of head-twitches induced by 5-HTP of mice (p<0.01). It can antagonize the inability of eyes opening and akinesia evoked by reserpine (p<0.05). In the depression model group, the morphology of neurons in the hippocampus is aberrant, and the expression of 5-HT2 and c-fos increase significantly in parietal cortex and hippocampus. However, SXY-006 improve the morphology of neurons in the hippocampus, and different SXY-006 groups had no changes in the expression of 5-HT2 and c-fos.Conclusion: The traditional Chinese medicine"SXY-006"exerts antidepressant effect probably throughâ‘ inhibiting the reuptake of monoamine in synaptic cleft or inhibiting monoaminoxidase,â‘¡protecting hippocampal neurons,â‘¢decreasing the expression of 5-HT₂ and c-fos.