Studies On Antidepressant Effect And Mechanism Of The Total Irioids Of Roots And Rhizomes Of Valeriana Jatamansi Jones Based On Gut-brain Axis

Objective Based on the brain-gut axis to explore the role and mechanism of the Total Irioids of Roots and Rhizomes of Valeriana jatamansi Jones(TIV)antidepression and improve depression with mild diarrhea,visceral hypersensitivity and other symptoms.Method 1.Valeriana jatamansi Jones herbs was extracted with 70% ethanol for 3 times and concentrated under reduced pressure to obtain alcohol extract.A large amount of water was used to disperse the alcohol extract and then purified by D101 macroporous resin.Eluted with pure water and 60% ethanol,successively,finally eluted with 95% ethanol and collected eluent.Concentrated and recovered ethanol under reduced pressure to obtain the extraction.Then TIV could be got by vacuum drying at 45 ?.Measured the content by UV spectrophotometry(UV)using Chlorovaltrate as a control.2.The mice depression model was established by orphaning combined with the chronic unpredictable mild stress(CUMS).The mice were modeling for 4 weeks and the success of modeling was verified by macroscopic observation,weight,suspension time experiment and sugar water consumption rate experiment.Fluoxetine(2.6 mg/kg/d),low(5.7 mg/kg/d),medium(11.4 mg/kg/d),and high(22.9 mg/kg/d)TIV were given respectively by administration intragastric.The anti-depression effect of TIV was verified by suspended tail immobility time experiment and sugar water consumption test after continuous administration for 2 weeks.Use enzyme-linked immunosorbent assay(ELISA)to evaluate content of serotonin(5-HT),norepinephrine(NE),substance P(SP)and corticotropin releasing factor(CRF)in both hippocampus and colon tissue.3.The fecal flora in the colon of mice was analyzed by using the 16 S rDNA amplification sequencing analysis technology at Alpha diversity,Beta diversity and different classification levels,respectively,so as to explore the changes in the intestinal flora structure of depressed mice and the regulatory effect of TIV on the intestinal flora structure of depressed mice.Result 1.After extracting,separatings and purifying 10.4kg of Valeriana jatamansi Jones herbs,the TIV content was 190 g.The content was 76.58±2.14% after detection by ultraviolet spectrophotometer.2.In the behavioral experiments after modeling,compared with the normal group,the mice in the model group,the positive group,the low,medium and high dose groups,the immobility time during 4 min suspension experiment extremely significantly increased(P<0.01),and the consumption rate of sugar water extremely significantly decreased(P<0.01).These indicated that the mouse model of depression was successfully replicated by CUMS method.After the treatment of TIV,compared with the model group,the immobility time of suspended tail extremely significantly reduced(P<0.01)and the consumption rate of sugar water extremely significantly increased(P<0.01)in the positive group and the high-dose TIV group;The immobility time of suspended tail significantly decreased(P<0.05),and the sugar water consumption rate significantly increased in the TIV medium dose group(P<0.05);The content of 5-HT significantly increased in the hippocampus of the positive group,TIV medium dose group and the TIV high dose group(P<0.01),but significantly decreased in the colon tissue of the positive group(P<0.01)and TIV high dose group(P<0.05);The content of NE increased in the hippocampal tissues of the TIV high-dose group(P<0.05);and decreased in colon tissues of the TIV medium-dose and high-dose groups(P<0.05);The content of SP significantly decreased in hippocampus of TIV medium and high dose group(P<0.01)and colon tissue of TIV high dose group(P<0.05);The content of CRF significantly decreased in the hippocampus of the positive group and high dose group(P<0.01),the TIV medium dose group(P<0.05)and the colon tissues in the positive group and the TIV high dose group(P<0.01),low dose and medium dose TIV group(P<0.05).3.The 16 S rDNA amplification and sequencing analysis technique was used to analyze the intestinal flora of mice.Although there is no significant difference in the diversity and abundance of intestinal flora in each group,there is a difference in relative abundance,especially the dominant bacteria,Firmicutes,Proteobacteria and Bacteroides.Combined with relevant reports and analysis of the relative abundance changes of Lactobacillus,Rumenaceae and Bacteroides,we speculate that this might be closely related to the occurrence of depression and TIV has a certain regulatory effect on the intestinal flora structure of depressed mice.Conclusion 1.TIV could correct depression and depression with mild diarrhea,visceral hypersensitivity.The anti-depression mechanism might be related to the improvement of neurotransmitters such as 5-HT,NE and the reduction of gastrointestinal motility.And the correction of visceral hypersensitivity mechanism might be related to the regulation of gastrointestinal by reducing the levels of 5-HT,NE,SP,and CRF neurotransmitters in the colon.2.The relative abundance changes of Lactobacillus,Rumenaceae and Bacteroides might be related to depression in intestinal flora,and TIV had a regulatory effect on the intestinal flora structure of depressed mice.