Protective Effect of Modified Sinisan on Depression-induced Liver Injury in Rat / 中国实验方剂学杂志

Objective:To study the protective effect of modified Sinisan on liver injury caused by chronic unpredictable mild stress (CUMS) combined with solitary nutrition method based on a depression model. Method:Forty-eight SD male rats were randomly divided into normal group, depression model group, fluoxetine group (1.58 mg·kg-1·d-1), and low, medium and high-dose modified Sinisan (3.67, 7.34, 14.68 g·kg-1·d-1) groups, with 8 rats in each group. After the administration of the model, the levels of alanine aminotransferase（ALT）, aspartate aminotransferase（AST） in serum and the levels of inflammatory factors tumor necrosis factor-α（TNF-α）, interleukin（IL）-1β, and IL-6 in liver tissues were measured by a biochemical kit method. Western blot was used to detect the expressions of cysteine aspastic acid-specific protease-3 (Caspase-3) and cleaved Caspase-3 in liver cells after intervention with modified Sinisan. Result:Compared with the normal group, the biochemical test showed that the levels of ALT and AST in the serum of the model group were significantly increased (P<0.05), and the levels of inflammatory factors TNF-α, IL-1β and IL-6 in liver tissue significantly increased (P<0.05). Compared with the model group, low, medium-dose modified Sinisan groups significantly reduced serum ALT, AST and inflammatory factors TNF-α, IL-1β and IL-6 levels (P<0.05). Western blot showed that compared with the normal group, the protein expression of Caspase-3 in model rat liver cells decreased, while the protein expression of cleaved Caspase-3 increased（P<0.05，P<0.01）. Compared with the model group, low, medium-dose modified Sinisan groups could up-regulate Caspase-3 protein expression, and down-regulated the expression of cleaved Caspase-3 protein（P<0.05，P<0.01）. Conclusion:Chronic stress-induced depression model can cause liver damage. Modified Sinisan can have the hepatoprotective effect by regulating the levels of various physiological, biochemical and inflammatory factor indicators, and inhibiting liver cell apoptosis.

Effects of Shugan Hewei Decoction and active substance fractions on behavior and neurotransmitter levels in hypothalamus of depression model rats / 中国中药杂志

To investigate the effects of Shugan Hewei Decoction and its active substance fractions on behavior and neurotransmitter levels in hypothalamus of depression model rats,and preliminarily explore its possible mechanism. Male SD rats were randomly divided into blank control group,model group,fluoxetine( positive control) group,Shugan Hewei Decoction high and low dose groups,high and low dose groups of three different substance fractions. After 3 weeks' CUMS and social isolation to induce models,intragastrical administration lasted for 7 d. Behavioral experiments( sucrose consumption test,open-field test,and forced swimming test) were then performed to evaluate the depression status of rats. Several neurotransmitters in hypothalamus of rats were determined by LC-MS/MS method,including dapamine( DA),norepinephrine( NE),serotonin( 5-HT),5-indoleacetic acid( 5-HIAA),γ-aminobutyric acid( GABA),and glutamic acid( Glu). As compared with the blank control group,the sucrose consumption was reduced( P<0. 01); the total distance and the number of crossing the central area were also significantly reduced( P< 0. 01,P< 0. 01),while the resting time increased significantly( P<0. 01); the forced swimming time was significantly prolonged( P<0. 01); DA,5-HT,NE,5-HIAA and GABA levels in hypothalamus were significantly reduced( P < 0. 01),while Glue level was significantly increased( P < 0. 01) in model group. As compared with the model group,all the above indexes had changes in fluoxetine group,Shugan Hewei Decoction whole recipe groups,volatile oils group,polysaccharides group,and terpenoids group( P<0. 01 or P<0. 05). Shugan Hewei Decoction whole recipe and its active substance fractions can improve the behavior of depression model rats and may exert anti-depression effects by regulating the content of neurotransmitters in the hypothalamus.

Active substance fractions and effects of Shugan Hewei Tang on hippocampal meurotransmitters in rat model of chronic stress-induced depression / 中国中药杂志

To study the antidepressant effect of Shugan Hewei Tang on chronic stress depression model rats, and select the effective substance fractions. Several male SD rats were randomly divided into 17 groups: blank control group, model group, positive control group(fluoxetine), Shugan Hewei Tang high and low dose groups, 6 high and low dose groups of different substance fractions. After modeling for 3 weeks and administration for 1 week, the effective substance fractions were selected according to the body mass and behavioral performance of SD rats in each group; several neurotransmitters in hippocampus of rats were determined by LC-MS/MS method, including norepinephrine(NE), serotonin(5-HT), 5-indoleacetic acid(5-HIAA), r-aminobutyric acid(GABA), and glutamic acid(Glu). Behavioral results after modeling showed that as compared with the blank group, the body mass growth of the model group was significantly reduced(P<0.01); the sugar water consumption was reduced(P<0.01); the distance between the open field and the number of crossing the central area were also significantly reduced(P<0.01, P<0.01); the resting time was increased significantly(P<0.01); and the forced swimming time was significantly prolonged(P<0.01), indicating that the depression model was effective. After intragastric administration, as compared with the model group, the above detection indicators of volatile oils, total polysaccharides and terpenoid in Fluoxetine, Shugan Hewei Tang groups were all changed(P<0.05 or P<0.01). The levels of NE, 5-HT and GABA in the hippocampus of the model group were significantly lower than those in the blank group(P<0.01), and the levels of 5-HIAA and Glu were significantly increased(P<0.01). As compared with the model group, neurotransmitters of the treatment groups were changed obviously or significantly(P<0.05 or P<0.01). Shugan Hewei Tang showed obvious anti-depressant effects, and the volatile oils, total polysaccharides and terpenoids acted as the main active substances. The mechanism of anti-depression may be related to its regulation of various neurotransmitter levels in the hippocampus.