| Objective:This thesis proposes to investigate the effects of different doses and isolated fractions of fructus Psoraleae corylifoliae and its salt-roasted products on the fecal morphology and blood in stool,intestinal morphology and barrier system,and intestinal flora of rats with ulcerative colitis from the perspective of the intestinal barrier using a model of ulcerative colitis,taking the clinical use of Psoralea and its salt-roasted products as the starting point of Chinese medicine and combining network pharmacology and molecular docking techniques.This study will provide a preliminary description of the changes in the efficacy of fructus Psoraleae corylifoliae before and after concoction in the treatment of ulcerative colitis and its related concoction mechanism,so as to enrich the connotation of fructus Psoraleae corylifoliae concoction,ensure the safety of clinical use,and also provide ideas and methods for screening effective drugs for the treatment of ulcerative colitis.Methods:1.Prediction of therapeutic targets for the treatment of ulcerative colitis with fructus Psoraleae corylifoliae based on network pharmacology: network pharmacology and molecular docking techniques were used to predict the potential active ingredients and possible therapeutic pathways of fructus Psoraleae corylifoliae.The network pharmacology and molecular docking techniques were used to predict the potential active ingredients and possible therapeutic pathways.Finally,the binding ability of the active ingredient to the core target was predicted by molecular docking techniques.2.Based on the difference in different doses of fructus Psoraleae corylifoliae and its salt-roasted products: the difference in the therapeutic effect of different doses before and after concoction was studied using a rat model of ulcerative colitis.The differences in the therapeutic effects of different doses of fructus Psoraleae corylifoliae before and after concoction were compared according to the differences in daily scores such as DAI,faecal properties and occult blood,colonic properties and inflammatory factors.3.Based on the isolation of different fractions of fructus Psoraleae corylifoliae and its salt-roasted products: the therapeutic differences of different fractions of fructus Psoraleae corylifoliae before and after concoction for ulcerative colitis disease were investigated in conjunction with a rat model of ulcerative colitis.The therapeutic advantages of the different fractions of psoralen in relation to the first part were also inferred.4.Cecum content sample collection and intestinal flora analysis based on Part II and Part III experiments: the differences in intestinal flora produced by the treatment of UC disease before and after tonicum concoction were analysed by various factors,including phylum differences,genus differences and species differences.The genera with significant differences,changes in improving Blank dominant genera and characteristic intestinal flora markers were also collated.Result:1.The experimental results showed that there were 661 common targets associated with the blood-entering component of the network pharmacology complement and ulcerative colitis disease targets,17 of which were core targets.The above targets were then imported into the KEGG database and three individual signalling pathways were collated and identified,involving a total of 12 experimental targets awaiting subsequent experimental validation.2.Through the experiment of each dose group of fructus Psoraleae corylifoliae and its salt-roasted products,according to the DAI score,fecal indexes,colonic tissue indexes and ELISA test indexes,it was confirmed that fructus Psoraleae corylifoliae had better therapeutic effect against UC rats prepared by TNBS method before and after concoction,and the therapeutic directions before and after concoction were different,but there were differences in therapeutic effect between the doses.3.Next,the groups of bone tonic and salt tonic were grouped together and found to have equally good therapeutic effects in each component.Subsequently,the protein and m RNA levels of the tonic lipid fractions were measured against 12 experimental targets,and it was basically determined that each group had its own superior pathway in the treatment of UC disease.4.Finally,the number of statistically significant differences in the genera between the treatment groups and the Blank and Model groups and the improvement in the dominant and unfavourable genera for the Blank group were analysed and collated,and it was hypothesized that the significant changes in the genera of the intestinal flora in each treatment group had a positive effect on the improvement of UC disease,and that there were some differences in the genera significantly changed before and after the preparation of fructus Psoraleae corylifoliae,which indicated that the preparation of fructus Psoraleae corylifoliae.This suggests that there is a difference in the genus of bacteria that changed significantly before and after the concoction of B.tonicum in the treatment of UC disease.Conclusion:Based on the above network pharmacological and animal experimental analyses,it was confirmed that psoralen has some feasibility in the treatment of ulcerative colitis,but the focus of the treatment of UC disease before and after concoction was not the same,and there were significant differences in the therapeutic effect between different doses,while the therapeutic effect was basically the same between different components,but because the dominant pathway of the effect of each component was not exactly the same,this provides a good basis for subsequent more precise compound research This provides a good basis for more precise compound studies.In subsequent studies of intestinal flora,significant differences were found between the treatment groups and the Blank and Model groups,and each treatment group was able to target both the dominant and unfavourable genera in the Blank group,providing a basis for further studies of the genetic changes in UC disease. |
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