Experimental Study On Antidepressant Effect Of Suanzaoren Decoction

Objective:To explore the antidepressant effect and mechanism of Suanzaoren Decoction,and to provide pharmacological basis for its clinical application.Methods:1.Pharmacodynamic study:（1）After 3 days of adaptive feeding,mice were divided into blank control group,fluoxetine group（20mg/kg）,high-dose Suanzaoren Decoction group（21.86g/kg crude drug）,medium-dose Suanzaoren Decoction group（14.57g/kg crude drug）and low-dose Suanzaoren Decoction group（7.29g/kg crude drug）according to their body weight,randomly.The control group was given distilled water of the same volume for 16 days.Open experiment,tail suspension experiment and forced swimming experiment were conducted on the 13th,14th and 15th day of administration respectively.（2）The chronic unpredictable mild stress model was established in rats.Sugar preference was used as the criterion for the success of CUMS.After successful modeling,rats were randomly divided into model group,fluoxetine group（10mg/kg）,high-dose Suanzaoren Decoction group（15.3g/kg crude drug）,medium-dose Suanzaoren Decoction group（10.2g/kg crude drug）,low-dose Suanzaoren Decoction group（5.1g/kg crude drug）.At the same time,blank control group was set up.Each group was given orally for 15 days,blank control group and model group were given.Distilled water of the same volume.Except for the blank control group,the other groups continued to be stressed for 14 days and recorded the weight of rats once a week.Sugar preference test was performed after the last administration.Three opening experiments were conducted before,after and 13 days after administration.2.Mechanisms:（1）The contents of 5-HT,NE and DA in hippocampus and cortex of mice were determined by ELISA.（2）The contents of5-HT,CORT,ACTH in serum and CRH in hypothalamus of CUMS rats were determined by ELISA.（3）The expression levels of 5-HT_1A receptor,GR,PKA,CREB and p-CREB in rat hippocampus were determined by RT-PCR.The experimental results were processed by SPSS21.0 statistical software.Results:1.Pharmacodynamic study:（1）Compared with the blank control group,the tail-suspension immobility time of mice in high-dose group and fluoxetine group was significantly shortened（p<0.01）;the tail-suspension immobility time of mice in middle-dose group,low-dose group were shortened（p<0.05）;the swimming immobility time of mice in high-dose group,fluoxetine group were significantly shortened（p<0.01）;the swimming immobility time of mice in the middle dose group of Suanzaoren Decoction was shortened（p<0.05）.（2）After 21 days,compared with the blank control group,the sugar preference（p<0.05）and weight gain（P<0.01）of model group,fluoxetine group,high-dose group of Suanzaoren Decoction,medium-dose group and low-dose group decreased.14 days after administration,compared with model group,sugar preference of rats in blank control group,fluoxetine group and high,medium and low dose groups of Suanzaoren Decoction increased significantly(（p<0.01）.The weight gain of rats in high-dose group increased significantly(（p<0.01）,while that of rats in fluoxetine group and medium-dose group of Suanzaoren Decoction increased significantly(（p<0.05）.In the opening experiment,compared with the blank control group,there was no significant difference in the movement distance between the fluoxetine group and the high,middle and low dose groups of Suanzaoren Decoction（p>0.05）;after the establishment of the model（before administration）,compared with the blank control group,the movement distance of the model group and the fluoxetine group was significantly reduced(（p<0.01）,and the movement distance of the high,middle and low dose groups of Suanzaoren Decoction was significantly reduced(（p<0.01）.After administration,compared with model group,the movement distance of rats in blank control group,fluoxetine group and Suanzaoren Decoction high,middle and low dose groups significantly increased(（p<0.01）.2.Mechanisms:（1）Compared with the blank control group,the contents of 5-HT and DA in hippocampus and cortex of mice in fluoxetine group increased significantly（p<0.01）,5-HT in hippocampus of mice in Zizyphus spinosa group increased（p<0.05）,and 5-HT in cortex of mice in Zizyphus spinosa spinosa group increased（p<0.05）.（2）The contents of 5-HT and DA in hippocampus and cortex of mice in fluoxetine group increased significantly compared with the blank control group（p<0.01）,and the contents of 5-HT in cortex also increased（p<0.05）.The level of 5-HT in hippocampus of mice in Suanzaoren Decoction group increased compared with the blank control group（p<0.05）,the content of 5-HT in cortex tended to increase.Compared with the model group,the serum 5-HT levels in the blank control group and fluoxetine group were significantly higher（p<0.01）,and the serum 5-HT levels in the Suanzaoren Decoction group were significantly higher（p<0.05）,while the serum CORT,ACTH and CRH levels in the hypothalamus were significantly lower in the blank group,Suanzaoren Decoction group and fluoxetine group（p<0.01）.（3）The expression of 5-HT_1A receptor and GR receptor in hippocampus of blank control group and fluoxetine group increased significantly compared with model group（p<0.01）,and that of 5-HT_1Areceptor and GR receptor in hippocampus of Suanzaoren Decoction group increased significantly（p<0.05）;the expression of PKA in hippocampus of blank control group,Suanzaoren Decoction group and fluoxetine group increased significantly（p<0.01）;The expression of CREB and p-CREB in hippocampus of Suanzaoren Decoction group increased significantly（p<0.01）,and the expression of CREB and p-CREB in hippocampus of Suanzaoren Decoction group increased（p<0.05）.Conclusion:1.Suanzaoren Decoction has certain antidepressant effect.Both Suanzaoren Decoction and fluoxetine can shorten the tail suspension immobility time and swimming immobility time of mice,and improve the sugar preference and weight gain of CUMS model rats.2.Suanzaoren Decoction can significantly increase the content of serum 5-HT and the expression of 5-HT_1A receptor in hippocampus of CUMS rats,suggesting that the antidepressant effect of Suanzaoren Decoction is related to 5-HT and 5-HT_1A.3.Suanzaoren Decoction and fluoxetine can significantly reduce the contents of CORT and ACTH in serum and CRH in hypothalamus of CUMS rats,and increase the expression of GR receptor gene,suggesting that the antidepressant effect of Suanzaoren Decoction is related to the regulation of HPA axis.4.Suanzaoren Decoction and fluoxetine can significantly increase the expression of PKA,CREB and p-CREB in hippocampus,suggesting that the antidepressant effect of Suanzaoren Decoction is related to the influence of c AMP-PKA-CREB signaling pathway.