Explore The Mechanism Of Jiaotai Wan In The Treatment Of Depression From The Perspective Of Intestinal Flora

Objective:Clarify the key target and action pathway of Jiaotai Wan in the treatment of depression,clarify the role of intestinal flora in the treatment of depression,further explain the antidepressant mechanism of Jiaotai Wan,and reveal the scientific connotation of the antidepressant effect of Jiaotai Wan.Methods:1.This paper combs the ancient and modern literature,systematically expounds the etiology,pathogenesis and syndrome distribution of depression,and expounds the common traditional Chinese medicine prescriptions for the treatment of depression.2.TCMSP and other databases were used to screen the active components of Jiaotai Wan and the chemical components of Jiaotai Wan were screened and extracted from tcmsp database and relevant literature.Pharmapper server and drugbank database were used to screen the potential targets of Jiaotai Wan for antidepressant effect.At the same time,the data of known disease targets related to depression were collected,and the network between the component targets of Jiaotai Wan and known disease related targets was constructed based on PPI protein interaction database.The key targets were selected according to the extended structure eigenvalues of the nodes.DAVID was used to analyze the main biological pathways associated with targets,and conduct pathway enrichment analysis for them.The top 3 core targets related to depression and their corresponding chemical components were molecularly docked with the help of Autodock vina 1.1.2 software.3.135 healthy male rats were randomly divided into 9 groups: blank group,model(CUMS)group,fluoxetine group,Jiaotai Wan high-dose group,Jiaotai Wan low-dose group,Coptidis Rhizoma high-dose group,Coptidis Rhizoma low-dose group,Cinnamomum cassia high-dose group and Cinnamomum cassia low-dose group,with 15 rats in each group.After one week of adaptive feeding,the rat model of chronic mild unpredictable stress depression was established.After the experiment,the feces of rats were collected,and the abundance of intestinal flora in feces of rats in each group was detected by 16 S r DNA amplicon sequencing.Results:1.Theoretical research on depression: depression belongs to the category of "Yu syndrome,epilepsy,globus hystericus,Baihe disease and visceral irritability".The etiology and pathogenesis are qi depression,phlegm turbidity,blood deficiency and so on.The syndrome types include liver qi stagnation syndrome,liver qi stagnation and spleen deficiency syndrome,phlegm qi stagnation syndrome,heart and spleen deficiency syndrome,liver and kidney yin deficiency syndrome,heart and kidney Disharmony Syndrome.The traditional Chinese medicine prescriptions commonly used by modern doctors to treat depression include Suanzaoren Decoction and Xiaoyao Powder,among which Jiaotai Wan is widely used because of its simple and good efficacy.2.19 active ingredients of Jiaotai Wan were screened,corresponding to 332 effective targets,3214 related disease targets,and a total of 148 intersection targets,mainly involving AKT1,IL6,VEGFA,MMP9,MYC,EGF,TLR4,PTEN,IL10 etc.target.Biological pathways include HIF-1 signaling pathway,IL-17 signaling pathway,Toll-like receptor signaling pathway and other inflammatory signaling pathways and PI3K-Akt signaling pathway.Molecular docking results showed that AKT1,IL6,VEGFA and their corresponding chemical component quercetin and berberine had strong interactions.3.Improvement effect of Jiaotai Wan on intestinal flora of depression model rats: α In terms of diversity,the Simpson value of the model group was slightly lower than that of the Jiaotai Wan high-dose group of and the Coptidis Rhizoma high-dose group.The Chao1 index and observed species of the model group were higher than that of the Jiaotai Wan high-dose group of and the Coptidis Rhizoma high-dose group.β In terms of diversity,NMDS diagram shows that the colonies of model group and traditional Chinese medicine group are clustered respectively;Species composition analysis showed that compared with the blank group,the abundance of Lachnospiraceae,Bacteroides and Blautia in the model group decreased,and the abundance of Ruminococcaceae increased;Compared with the model group,the abundance of Lachnospiraceae,Bacteroides and Akkermansia in Jiaotai Wan group increased,while the abundance of Ruminococcaceae decreased;LEf Se analysis showed that the differential flora of Jiaotai Wan group were Lachnospiraceae and Akkermansiaceae.Conclusions:1.Depression belongs to the category of "Yu syndrome and visceral irritability" in traditional Chinese medicine.Its etiology and pathogenesis are complex and its syndrome types are diverse.There are many traditional Chinese medicine prescriptions that can treat depression.Jiaotai Wan can play an antidepressant role by regulating neurotransmitters,inflammatory response and brain-derived nerve factors in rats.2.Jiaotai Wan may play an antidepressant role by regulating inflammatory signal pathways such as HIF-1 signal pathway,IL-17 signal pathway,toll like receptor signal pathway and PI3 K Akt signal pathway through nine depression related targets such as AKT1,IL6,VEGFA,MMP9,MYC,EGF,TLR4,PTEN and IL10,so as to participate in the process of regulating BDNF synthesis,anti inflammation and affecting synaptic plasticity.It shows the antidepressant mechanism of "multi-component,multi-target and multi-channel" of Jiaotai Wan.3.The research shows that Jiaotai Wan can regulate the inflammatory reaction to achieve the purpose of anti depression,and the level of inflammatory factors is related to the abundance of intestinal flora.Different doses of Jiaotai Wan,Coptidis Rhizoma and Cinnamomum cassia can change the abundance of intestinal flora in rats to varying degrees.This shows that Jiaotai Wan may play an antidepressant role by reducing the abundance of pathogenic bacteria,increasing the abundance of beneficial bacteria,improving the structure of flora.