Screening And Mechanism Of Traditional Chinese Medicine Monomer For Inhibiting Ulcerative Colitis In Mice

Inflammatory bowel disease（IBD）,including 2 chronic relapsing inflammatory diseases:Crohn’s disease（CD）and ulcerative colitis（UC）.In recent years,the incidence of IBD has increased in many countries around the world.IBD has become a recognized global disease.The main difference between UC and CD is where the inflammation occurs and the inflammation itself.UC is a persistent inflammation of the colonic mucosa and submucosa.It usually first involves the rectum and then gradually spreads throughout the colon.CD usually involves the terminal ileum,cecum,and is associated with complications such as abscesses,fistulas,and strictures.Studies have shown that UC can lead to an inflammatory response and gut barrier dysfunction.At present,the symptoms of UC are mainly relieved by drug therapy,such as the use of aminosalicylic acid,glucocorticoids,immunosuppressants,and non-steroidal anti-inflammatory drugs.However,issues such as adverse reactions and drug resistance arising from these drug treatments remain to be resolved.Therefore,the most urgent task is to develop new safe and effective treatments for the prevention and treatment of UC.In recent years,more and more natural compounds derived from plants,food,and Chinese herbal medicines have become an alternative choice for the treatment of chronic inflammatory diseases（such as UC）because of their unique advantages such as fewer toxic side effects,definite curative effect,and reduced recurrence rate.Eight natural compounds from different sources,named jugone,borneol,puerarin,kaempferol,sesamin,royal jelly acid,pogostone and liquiritin,that are Chinese medicine monomers.They all have potential anti-inflammatory and anti-tumor effects.However,there are few studies on its protective effect and mechanism of action on UC.In order to find out effective traditional Chinese medicine monomers that can treat UC and explore its protective mechanism on UC,we conducted the following experiments:In this experiment,an animal model of colitis was established by freely drinking water containing 2.5% dextran sulfate sodium（DSS）in mice.During the modeling period,different traditional Chinese medicine monomers were administered daily to observe whether different traditional Chinese medicine monomers had preventive and control effects on the established animal model.After 7 days of modeling,the weight of the mice,the disease activity index（DAI）of the mice,the length of the colon in the mice,the histopathological observation of the colon and the degree of tissue damage were scored to explore whether different traditional Chinese medicine monomers could relief of disease severity in mice with colitis.The results showed that among 8different Chinese medicine monomers,juglone could reduce the degree of pathological damage,the shortening of colon,the degree of colon damage and the DAI score in mice with colitis.At the same time,juglone debased the expression levels of pro-inflammatory cytokines TNF-α and IL-1β,and enhanced the expression level of anti-inflammatory cytokines IL-10.Subsequently,we studied the protective mechanism of juglone on DSS induced ulcerative colitis in mice.Moreover,juglone can restrain the DSS-induced decline in the expression of tight junction proteins such as ZO-1 and occludin,and enhance the thickness of the intestinal mucosal barrier,so as to protect the function of the intestinal mucosal barrier.We also found that Juglone can restrain the infiltration of intestinal macrophages,adjust the polarization of M1/M2 macrophages.In addition,we found that juglone can reduce the phosphorylation levels of p65 and p38,inhibit the activation of NF-κB,MAPK,and NLRP3 inflammatory pathways,and at the same time increase the expression of PPAR-γ,thereby exerting its anti-inflammatory effect..In conclusion,juglone has a certain protective effect on DSS-induced colitis,which lays a theoretical foundation for the prevention and treatment of UC in the future.