The Mechanism Of Scutellaria Baicalensis Inhibiting The Cancerization Of Ulcerative Colitis Based On The Homeostasis Of Intestinal Microbiota

Ulcerative colitis(UC)is a chronic inflammatory disease of the intestinal tract with unknown etiology,which is one of the three high risk factors of colorectal cancer(CRC).The process of UC developing to CRC is usually considered to be related to the repeated inflammation-repair of the intestinal mucosa in the course of the disease.Previous evidences suggested intestinal microbiota play an important role in the development of CRC.Scutellaria baicalensis is significantly effective on the treatment of ulcerative colitis and the improvement of CRC prognosis in the clinical practice,while the biotransformation of gut microflora may be crucial in affecting the metabolic process and efficacy of Scutellaria baicalensis.Based on the homeostasis of intestinal microbiota,this study explored the mechanism of Scutellaria baicalensis inhibiting colitis-associated cancer(CAC).1.Advances in intestinal microbiota-mediated CAC and Scutellaria baicalensis for medicinal purposesThis section described epidemiological survey and causes of CAC,and summarized the CAC treatment and mechanism,and provided a detailed review of intestinal microbiota-mediated CAC and Scutellaria baicalensis for medicinal purposes based on massive literatures.Meanwhile,the topic basis and design of this study were presented,which offered a theoretical guidance for the development of experiments in this thesis.2.Pharmacodynamics investigations of Scutellaria baicalensis on CAC model miceCAC model was established using carcinogen azoxymethane(AOM)and inflammatory agent dextran sodium sulfate(DSS)on C57BL/6 mice.45 mice were randomly divided into three groups,including normal group(15),model group(15)and Scutellaria baicalensis group(15).Disease activity index(DAI)of mice were evaluated,colon tissue morphology was observed and levels of inflammatory cytokines were determined by enzyme linked immunosorbent assay(ELISA)in this section,for the pharmacodynamics investigations of Scutellaria baicalensis.Compared with model group,Scutellaria baicalensis can effectively improve the mice performance,withstand the atrophy of colon tissue,and decrease the numbers and sizes of tumor.Furthermore,colonic dysplasia was relieved and levels of inflammatory cytokines were reduced.Therefore,Scutellaria baicalensis could effectively alleviate the development of CAC.3.Effects of Scutellaria baicalensis on the intestinal microbiota of CAC model miceThe fresh intestinal contents of mice from normal group,model group and Scutellaria baicalensis group were taken for DNA extraction.The genomic DNA of each sample was used as a template to amplify the segment of V3 region of 16 S rDNA gene,which was purified by Gel/PCR DNA Fragments Extraction Kit.16 S rRNA gene sequencing was performed on mice intestinal microbiota,and the mechanism of mechanism of Scutellaria baicalensis inhibiting CAC was explored from the perspective of gut microflora.The model mice had significant microflora differences in community richness and diversity compared with the normal ones,as well as the ones after the intervention of Scutellaria baicalensis.It showed that Scutellaria baicalensis could regulate the composition of intestinal microbiota in the pathological state of CAC,increasing the numbers of beneficial bacteria and reducing harmful ones.The effects of Scutellaria baicalensis on the intestinal microbiota of CAC model mice may be related with the regulation of intestinal microbial communities,in the combination of efficacy evaluation.4.Biotransformation of main constituents of Scutellaria baicalensis with mice intestinal microbiotaThe suspension of intestinal microbiota was prepared by taking the fresh intestinal contents of mice from normal group,model group and Scutellaria baicalensis group.To simulate the vitro intestinal environment,the suspension was mixed with Scutellaria baicalensis extract,then cultured at 37? anaerobically.Samples were taken at different time points and analyzed by HPLC after preparation in order to observe biotransformation of main constituents of Scutellaria baicalensis with mice intestinal microbiota.The results displayed that intestinal microbiota of the model mice were relatively inefficient in the metabolic process,meanwhile this terrible state could be improved after the intervention of Scutellaria baicalensis.It indicated Scutellaria baicalensis could regulate the structure of intestinal microbiota,which in turn affected metabolic transformation of itself,so as to alleviate the development of CAC.5.Conclusion and prospectsIn this study,the mechanism of Scutellaria baicalensis inhibiting CAC was explored based on the homeostasis of intestinal microbiota,which is the priority herb in the treatment of CRC.By establishing the AOM/DSS mice model,the inhibiting effect of Scutellaria baicalensis on CAC was verified.Homeostasis of intestinal microbiota may be the key biological foundation of this inhibiting effect,and the interaction between gut microflora and Scutellaria baicalensis may be the important mechanism of Scutellaria baicalensis on CAC.This study will be helpful for data support of the treatment of of Scutellaria baicalensis on CAC in clinical practice,providing some scientific evidences for the treatment of CAC with microbial intervention.