Study Of Anti-inflammatory Effect And Mechanism Of Flavonoid Derivatives In Ulcerative Colitis

Ulcerative colitis(UC)is a kind of inflammatory bowel disease(IBD),which has the characteristics of long course,high recurrence rate and easy canceration.In recent years,the incidence of UC in China has increased rapidly.It seems urgent.Based on the chemical method of 1,8 diazepine and azaflavones,our research group synthesized 59 derivatives for the first time in the early stage.Taking flavonoid derivatives as the research object,we constructed a cell inflammation model and screened out The flavonoid derivatives with the best anti-inflammatory effect were used to explore the anti-inflammatory mechanism of flavonoid derivatives through the mouse UC model.A cell model was constructed in vitro to evaluate the anti-inflammatory ability of flavonoid derivatives.Mononuclear macrophage RAW264.7 was used to construct a cellular inflammation model to evaluate the anti-inflammatory ability of flavonoid derivatives.Lipopolysaccharide(LPS)was used to induce cells to establish the model of cellular inflammation,and the related inflammatory indexes were detected.At the concentration of10 μ M,derivative B17 inhibited the production of nitric oxide(NO)by 64.56%,significantly inhibited the level of related inflammatory factors,tumor necrosis factor TNF-α was68.58pg/m L,inflammatory factors IL-1 β,IL-6 and IL-8 were 2.43pg/m L,3.10pg/m L and22.37pg/m L,respectively,showing good anti-inflammatory effects.In the study of the antiinflammatory mechanism of derivative B17,it was found that B17 inhibited NF-κ B pathway by inhibiting the phosphorylation levels of NF-κ Bp65 and I κ B α,and had related antiinflammatory effects on MAPK.The phosphorylation levels of p38 and ERK1/2 were also inhibited.In the in vivo evaluation of derivative B17,a mouse model of ulcerative colitis induced by sodium dextran sulfate(DSS)was used to evaluate its anti-inflammatory effect.Flavonoid derivative B17 had a good therapeutic effect on colitis induced by DSS.Compared with the model group,the middle and high dose group of B17 prolonged the length of colon by 10.19%and 20.55%,respectively.The disease activity index(DAI)decreased by 27.8% and 33.3%,respectively.The results of HE staining showed that derivative B17 significantly improved the symptoms of colonic mucosal injury in UC mice.Compared with the positive drug group,the middle and high dose group of B17 decreased the levels of TNF-α,IL-1β and IL-6 in the serum of mice.Compared with the model group,the high dose group of B17 reduced the phosphorylation levels of NF-κB p65 and IκBα by 67.66% and 60.0%,respectively,and the levels of MAPK p38 and ERK1/2 in the high dose group of derivative B17 were 58.64% and32.40% of those in the model group,respectively.Derivative B17 can treat UC mice by inhibiting the expression of NF-κB and MAPK signal pathway related proteins in colon tissue.The changes of intestinal microflora abundance of UC mice were detected.After the treatment of derivative B17,the decrease of intestinal flora abundance of B17 mice was improved.Derivative B17 may improve the intestinal flora of mice to some extent while relieving ulcerative colitis in mice.In conclusion,the derivative B17 exhibited good anti-inflammatory effects both at the cellular level in vitro and at the animal level in vivo,and its mechanism of action was closely related to the inhibition of the expression of NF-κB and MAPK-related proteins.Microflora improves ulcerative colitis.In the future,we will further explore the related mechanism of its anti-inflammatory effect and the role of the improvement of intestinal flora in it.