polygala is a well-known traditional Chinese medicine used as an expectorant , tonic, sedative and preventing dementia agents. It was recorded in 《Shennong's Herbal》 and classified as high grade. In view of protophase research, It was found that Polygala play important part in antidepression as one ingredient of kai xinsan. In order to clarity active substance and mechanism of polygala on anti-depression the further, methods of chemistry and pharmacology were combinded to study polygala systematically.Through routine ethanol gradient elution, adsorption of macroporous resin, gradient elution of water and ethanol, YZ-30,YZ-50,YZ-70 and YZ-95 were gained.They were detected by HPLC to analyze the chemical composition initially.classic mice suspend tail and force swimming models were combined to preliminary screen YZ-30,YZ-50,YZ-70 and YZ-95 on anti-depression. The results indicated that YZ-30, YZ-50 show apparent antidepressant effect. The time dose dependent experiment was observed to screen antidepressant effect of YZ-30 and YZ-50. It was demonstrate that YZ-50 play important role in antidepression.YZ-50 was selected to research the antidepressant mechanism of action. The effects of YZ-50 on adrenergic systems were estimated preliminarily by yohimbine-induced lethality tests, the antagonism of high dose of apomorphine. Adopted rat chronic stress combined with raise isolated model, the effect of YZ-50 on rat behavior, HPA axis, Apoptosis of hippocampus neuron, the expression of BDNF and TrkB was researched. Consequence indicated that theactive parts of polygala can increase rat body weight, the rate of consumption of julep,level and vertical scores. To some extent, YZ-50 can improve depressant condition of rat; antagonize the hyperfunction of HPA axis to normalization; promote the Apoptosis-resistant gene expression of Bcl-2, while decrease the Apoptosis- stimulative gene expression of Bax to ease the damage of neuron caused by chronic stress and the happen of apoptosis ; advance the up-regulation expression of BDNF and its receptor TrkB mRNA.To identify active substance of the active site of YZ-50, HPLC-MS and everted intestinal sac model was linked to manifest. According to the purity of chromatographic peak and the data of mass-spectrum, It is presumed that the major ingredients of intestinal absorption were oligosaccharide esters and a small quantity of xanthenone,which were sibricoseA1,sibricoseA6, reinioseA and so on. The analysis of concrete structure and ascription depended on profound study.Finding demonstrate that the YZ-50 play its obvious antidepressant effects and ameliorate depressant condition by influencing monamine nervous function, resisting the hyperfunction of HPA axis, facilitating expression of Bcl-2 and reducing the expression of Bax to grow downwards the apoptosis of neuron in the hippocampus area of rat, up-regulating the expression of BDNF and TrkB mRNA to reinforce nutrition of neuron. |