To Explore The Effect Of Dahuang Mudan Decoction And Its Active Components In The Prevention And Treatment Of Inflammatory Associated Colorectal Cancer From TLR4/MyD88/NF-κB-p65 Signal Pathway

Objective: Firstly,to establish a transformation model of colonic non-classical inflammatory cancer for exploring the effect of Dahuang Mudan Decoction on the evolution of colitis cancer and its mechanism of action.After that,to study the effective components of Paeonol(Pae)and Rhubarb in the water extract of Dahuang Mudan Decoction(DHMD)The role of acid(Rhein)in the process of inflammation.Method: 1.The colorectal cancer model of mice transformed by non-classical inflammatory cancer was copied according to the AOM/DSS method.Then,in the process of model-making,the mice were treated with rhubarb peony decoction the physical condition and activity of the mice were carefully observed throughout the experiment.First of all,the expression of IL-1β、IL-6、IL-10、TNF-α cytokines in mouse serum was detected,after that,the expression of TLR4 、 MyD88 and NF-κB-p65 proteins in colorectal tissues was detected.2.To cultivate the Caco-2 cell seeding plate,and when the cells are in the logarithmic phase of the growth phase,immediately perform lipopolysaccharide(LPS)stimulation and induction modeling and the co-incubation of Pae,Rhein and LPS to treat the relevant cytokines in the cells.To measure and detect apoptosis of the treated cells,and to detect the expression level of related proteins in the cells.3.Results: After AOM/DSS stimulation,the mice showed weight loss,blood stool and anus.Furthermore,the expression of these factors in serum of IL-1β、IL-6、TNF-α mice increased and the expression expression IL-10 anti-inflammatory factors decreased,and the expression of TLR4、MyD88、NF-κB-p65 protein increased significantly.Through DHMD treatment,the weight loss of mice was controlled and the symptoms of colon lesions were improved.In addition,the expression of proinflammatory factors and related proteins was lower than that of the model group,IL-10 the opposite was true.The expression of pro-inflammatory factors in cells induced by LPS stimulation increased significantly,but the expression of IL-10 decreased.Moreover,the expression level of related proteins increased significantly.And that,the cells were damaged badly and the apoptosis rate was higher.On the contrary,On the contrary,cells Pae、Rhein co-incubated with LPS,not only has the expression of these proinflammatory factors been inhibited,but the expression of proinflammatory factors has also been improved.Furthermore,it also inhibited the expression of related proteins and reduced apoptosis.Conclusions: DHMD has a relieving effect on the inflammation of the colon,can reduce the inflammatory response,and reduce the incidence of inflammatory cancer transformation on the colon tissue,and it may be caused by regulating the TLR4/MyD88/NF-κB-p65 signaling pathway.The Pae and Rhein,the active ingredients of DHMD,can improve cell inflammation induced by LPS,and can also inhibit cell damage caused by LPS and reduce cell apoptosis.