Study On The Treatment Of Ulcerative Colitis With Cottonseed Peptides And Probiotics Complex

Ulcerative colitis(UC)is a chronic inflammatory bowel disease of unknown etiology.Current drug therapies of UC have serious side effects which may lead to liver and kidney damage,and long-term use may cause adverse effects such as nausea and dizziness.Therefore,it is essential in the search for safer and more effective new drugs for UC treatment.Some studies have shown that food-derived active substances such as small-molecule peptides and probiotics are effective in the treatment of UC.In this study,based on the previous combination of peptides and probiotics for UC treatment,a new cottonseed peptides and probiotics complex was developed to explore its effectiveness and mechanism for UC treatment.The details are as follows.(1)We used C57BL/6J mice as model animals to investigate the therapeutic effect of cottonseed peptides and probiotics complex on DSS-induced ulcerative colitis: this study used cottonseed peptide and probiotics complex administration to establish a UC mouse model using dextran sodium sulfate(DSS).The model fully replicated the main pathological features and clinical manifestations of UC,which caused weight loss,diarrhoea,blood in stool and depression,colon damage,increased inflammation and decreased antioxidant levels in experimental mice.The results showed that the UC model mice treated with 260 mg/kg,520 mg/kg and 780 mg/kg of cottonseed peptides and probiotics for 8 days significantly improved the symptoms of ulcerative colitis in mice.The results showed that there was no significant change in the index of other organs except for the liver index.HE staining showed that the colonic mucosa was heavily damaged after DSS treatment and there was a large infiltration of neutrophils.After administration of the treatment,there was a reduction in cupped cell damage and a small amount of neutrophil infiltration with a dose relationship.After treatment with cottonseed peptides and probiotics complex,the expression levels of SOD and CAT enzymes increased,while the expression levels of inflammatory factors decreased significantly.This suggested that the cottonseed peptides and probiotics complex alleviated DSS-induced ulcerative colitis mainly through antioxidant and antiinflammatory effects.(2)High-throughput sequencing was used to study the species and abundance of intestinal flora in mice: after the last gavage for 24 h,three samples of mouse cecum contents were taken from each group for analysis,and the sequencing region was the V3-V4 region of bacterial 16 s r DNA.The results revealed that the cottonseed peptides and probiotics complex enhanced the diversity and abundance of intestinal microorganisms in mice and ameliorated the abnormalities of intestinal microflora in DSS-induced mice.In addition,administration of the treatment significantly increased the levels of dominant flora and decreased the harmful flora.which suggested that it show good promise in the treatment of ulcerative colitis.(3)A network pharmacology and molecular docking based approach to predict the mode of interaction of cottonseed monomeric peptides on potential targets in ulcerative colitis: the database was used to screen potential targets for monomeric peptide intervention in ulcerative colitis and the three most relevant core targets were obtained.Molecular docking techniques were used to demonstrate that the binding sites of the monomeric peptides to the core targets were mainly concentrated on the surface of the hydrophobic depressed receptor molecules and resulted in hydrogen bonding and hydrophobic interactions.It can be inferred that the monomeric peptide attenuates ulcerative colitis by interacting with the TNF/JAK2 target protein.In conclusion,we verified at the animal level that cottonseed peptides and probiotics complex mainly alleviated the symptoms of DSS-induced ulcerative colitis through anti-inflammatory,antioxidant and intestinal flora regulation.We used network pharmacology and bioinformatics techniques to analyse the interaction mode of cottonseed peptides on the core targets of ulcerative colitis.This study not only broadens the application of small molecule peptides and probiotics,but also provides new ideas for the treatment of ulcerative colitis.