Researches On Substance Basis And Mechanism Of Antidepressive Chinese Medicine Formula Kai-xin-san On Regulation Of Neurotrophic Factors

Depression incidence is increasing continuously due to intensifying social competition and pressure, which has caused great harm to people health. So the treatment of depression has become a major subject to medical workers.In chapter one, research progress of depression were summarized in recent years, from the aspect of the pathogenesis of depression, depression etiology, pathogenesis, clinical and mechanism with Traditional Chinese medicine. The history and moder researches of Kai-Xin-San (KXS) series formulae were also reviewed here.In chapter two, the study aimed to reveal the anti-depressive mechanism of Kai-Xin-San (KXS) series formulae on chronic unpredictable mild stress (CUMS) treated mouse via regulation of neurotrophic factor system. Firstly, depressive animal model was created by applying a series of stress procedures on mice and the depressive-like mice were treated with KXS series formulae afterwards. It was found that KXS series formula exerted significant anti-depressive effect on CUMS treated depressive mouse model in presence of increased sucrose consumption, swimming time and weight. Meanwhile, in the cerebral cortex and hippocampus, the amounts of neurotrophic factors, NGF and BDNF, and the expression of the corresponding receptors, were both up-regulated after the treatment of KXS series formule. One ratio named D-652, with the higher amounts of Ginseng Radix et Rhizoma and Polygala, exerted the best effect. Therefore, regulation of neurotrophic factor system might be one of important active targets for anti-depression effect of KXS.In chapter three, the qualtiy control of KXS extract by determining the amout of Ginsenoside Rbl, Rgl, Re,3,6’-disinapoyl sucrose, Polygalaxanthone Ⅲ, α-asarone, β-asarone, Pachymic acid, which were identified as active compounds on neuronal system by using HPLC-DAD-TQ mass system. Meanwile, the lower limit of each compound was set up. Besides, the total aqueous extract of KXS (D-652) was separated by macroporous resin separation with ethanol with series concentration. Six fractions were acquired afterwards.In chapter four, the study aimed to explore the anti-depressive mechanism of Kai-Xin-San (KXS) via neurotrophic factor expression on rat astrocyte primary culture and rat glioma cell line. Rat brain astrocyte primary culture was created from postnatal 1 day rat. Afterwards, the culture was treated with different drugs, including KXS formula extracts, single herb extracts, fractions and active compound groups. Then, qPCR analysis was applied for the evaluation of neurotrophic factor expression. It was found that the expression of neurotrophic factors could be enhanced by KXS formula, Ginseng extract,70% and 90% ethanol fractions and active compounds including Rbi, Re, Rgi, which implied that KXS might exert its anti-depressive effect via up-regulation of neurotrophic factors and Ginseng Radix et Rhizoma, ginsenosides might be the active single herb and compounds, respectively...