Research On Antidepressive Mechanism Of Chaiyuwendan Decoction Based On The Gut-Brain Axis

Objective:To evaluate the pharmacological effect of chaiyuwendan decoction on depression behavior;The mechanism of chaiyuwendan decoction in treating depression was studied based on brain-gut axis signaling pathway.Method:Using the random number table method 60 SD male rats were randomly divided into normal group,model group,the Chaiyuwendan decoction-high-dose group(hereinafter referred to as chai-high group,similarly hereinafter),Chaiywendan decoction-low dose group(hereinafter referred to as chai-low group,similarly hereinafter),probiotics,fluoxetine group.The rat depression model with Chronic Unpredictable Mild Stress(CUMS)building method within 21 days was in random and none repetition,combined with single cage feeding set up,with behavioral changes as the depression model rats evaluation index;Amplification sequencing of v3-v4 region of 16S rRNA,brain tissue samples of depressed rats,cecum tissue,serum and feces were studied.ResultsBehavioral changes:compared with the normal group,the consumption of sugar and water,the total distance to the open field level and the center residence time of the open field in the model group(P<0.05)were reduced significantly.Compared with the model group,rats in chai-high group,chai-low group,probiotics group and fluoxetine group had significantly increased sugar water consumption,total distance to open field level and center residence time in open field(P<0.05).Pathological changes:compared with the normal group,a large number of intestinal glands were closely arranged in the cecum tissues of rats in the model group,accompanied by intestinal gland rupture,increased infiltration of eosinophilic granulocytes,and hyperchromatic cytoplasm.After treatment,eosinophil decreased in each drug group compared with the model group.Changes of neurotransmitters in the brain of rats:compared with the normal group,5-HT serumt content of rats in the model group was reduced significantly,the serum ACTH content was significantly increased,and the expression level of hippocampal BDNF mRNA was decreased significantly(p<0.01).Compared with the model group,the 5-HT content in chai-high group,chai-low group,probiotics group and fluoxetine group increased significantly(P<0.05),and the serum ACTH content decreased significantly(P<0.05,P<0.01).The expression level of BDNF mRNA in hippocampus of chai-high group and fluoxetine group increased significantly(p<0.01).No significant change in the expression of BDNF mRNA in the probiotic group(P<0.05).Changes of intestinal flora:Alloprevotella bacteria were found in the model group,and none of this bacteria were found in other groups.In each drug group,the relative abundance of Ruminococcaceae bacteria was increased after administration,while the relative abundance of this bacteria was not increased in the model group.In the Chai-high group,the abundance of bacteria was significantly increased with Ruminococcaceae and the abundance increased significantly;in the Chai-low group,Clostridia and Lachnospiraceae were significant species,and the abundance was significantly increased.Conclusion:1.The CUMS model was successfully established,and the CUMS method could induce depression-like behavioral changes in rats.Both the chai-high group and the chai-low group could improve depressive behaviors.2.The treatment of chaiyuwendan decoction can improve the diversity and structure of intestinal microflora in CUMS rats with depression,Ruminococcaceae and Lachnospiraceae increased in chai-high and chai-low groups,were found highly correlated with short-chain fatty acids.3.Chaiyuwendan decoction can regulate intestinal flora,improve intestinal permeability,affect intestinal mucosal barrier,reduce inflammation and improved depressive behavior was closely related to the gut-brain axis signaling pathway.