Research On Relieving Effect Of Puerarin On Ulcerative Colitis

Inflammatory bowel disease(IBD)is a lifelong chronic intestinal disease.More than 20% of IBD patients develop colorectal cancer(CRC).It has evolved from a westernized disease to a global disease,and the number of cases is expected to reach1.5 million in China by 2025.The development of IBD leads to intestinal obstruction,intestinal perforation and malnutrition,and more severe cases involve hepatobiliary inflammation,arthritis and skin diseases.Many factors contribute to the development of IBD,such as intestinal mucosal immune imbalance mediated by Th17 and Treg cells,dysfunction of bile acid and amino acid metabolic pathways,and intestinal flora disorder characterized by increased abundance of Enterobacteriaceae and decreased abundance of Firmicutes.Puerarin is a kind of isoflavones with biological activities such as anti-inflammatory,anti-cancer and improving cardiovascular and cerebrovascular functions.In this study,microbial sequencing and metabolomics technology were used to explore the protective mechanism of puerarin on ulcerative colitis.Key findings were as follows:Puerarin can restore colonic length and reduce colonic recess injury in mice with ulcerative colitis;histological scores and disease activity index scores decreased;the concentrations of pro-inflammatory cytokines IL-1β,IL-6 and TNF-α were inhibited.reduce fecal water content,improve diarrhea,relieve colitis.Pueraria increased the diversity of intestinal microorganisms,and inhibited Listeria,Alistipes,Prevotella copri,Enterobacteriaceae,Veillonella and other inflammatory pathogens.It promoted the development of bacteria such as S24-7(a bacteroides),and increased the level of Lactobacillaceae,Erysipelotrichacea,Bacteroidaceae,Deferribacteraceae and Prevotellaceae.Therefore,the regulation of colitis mice microbial ecological balance and relieve colitis.Puerarin changes the levels and metabolic pathways of intestinal metabolites in colitis mice.It increases levels of 6-hydroxyniacin,guanosine and 4-hydroxybenzoic acid to regulate niacin and niacinamide metabolism,pyrimidine metabolism and panquinone synthesis pathway.At the same time,the levels of longchain fatty acids(dodecanediic acid,docosahexaenoic acid,isooleic acid,oleic acid)and medium-chain fatty acids(azelaic acid,sebacic acid)were increased by the intervention of kudarin.Puerarin alone and puerarin and tryptophan together could restore colon length.Puerarin decreased histological score and disease activity index score by alleviating colonic recess injury.Puerarin group and puerarin combined with tryptophan group could regulate the levels of 5-hydroxytryptamine and indolol in the tryptophan pathway,niacin,niacinamide and 6-hydroxyniacin in the niacin pathway,and lysine and piperidinic acid in the lysine pathway.In addition,the effects of puerarin group alone on metabolites and pathways of rat colitis: regulates the metabolic levels of adenosine,inosine(purine metabolism),alpha-linolenic acid(polyunsaturated fatty acid metabolism),glutamine(glutathione metabolism),n-acetylneuramic acid,n-acetyl-Dglucosamine(amino sugars and nucleotide sugars metabolic pathways).These metabolites are the raw materials for the synthesis of vitamins,amino acids and fatty acids.Next,the effects of puerarin group and puerarin combined with tryptophan group on intestinal movement in rats with ulcerative colitis were studied.The results showed that the two groups of substances up-regulated the expression of AQP-3 aquaporin in colon and decreased the water content in stool.Reduce fecal p H and intestinal permeability;Prolonging colon propulsion time and gastrointestinal passage time can improve diarrhea symptoms.At the same time,the expression of serotonin transporter SERT is up-regulated,which terminates the function of serotonin and reduces the extracellular level to inhibit the uptake of 5-HT by intestinal mucosal tissue and relieve intestinal dysmotility.Supplementation of tryptophan increased the level of its metabolite 5-HT in the intestinal cavity and tissues,resulting in a less significant effect of combined intervention on intestinal dyskinesia.