Study On The Efficacy And Mechanism Of Kuijie Oral Decoction In The Treatment Of Ulcerative Colitis With Internal Damp-heat Type

Purpose:By observing the Ding’s Herb Oral agent Prescription in the treatment of ulcerative colitis model in mice intestinal inflammation,evaluate the curative effect of oral side dings and supervising,the and the use of western blot method prove its effect on the treatment of UC probably through cut the level of IL-6,IL-17 and TNF alpha.Material and method:1.Retrieve the database of traditional Chinese medicine and chemical composition of the Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences(http://www.organchem.csdb.cn)and the pharmacology database of traditional Chinese medicine system(http://tcmspnw.com).Has been reported in the chemical composition.The ADME/Tox virtual computing system was used to screen the potential active ingredients in the Dingkuijie Oral Formula.The pharmacophore model was used to calculate the interaction strength between each component and the corresponding target based on Support Vector Machine(SVM)algorithm and Random Forest(RF)algorithm.SVM ≥ 0.8 and RF ≥ 0.7 were used as screening conditions for virtual prediction.The potential targets of each active ingredient in the Ding’s Herb Oral agent Prescription.Multiple database search results are integrated to collect targets related to UC development,development,and treatment.The potential target of Ding’s Herb Oral agent Prescription and the target of UC were used as PPIs respectively to construct an interaction network between the two,and a target with significant significance was selected,and then Ding’s Herb Oral agent Prescription was selected.Potential targets for the treatment of UC.2 Forty female C57BL/6J mice were randomly divided into five groups: blank group,model group,mesalazine group,low dose group of Ding’s Herb Oral agent Prescription and high dose group of Ding’s Herb Oral agent Prescription.8 in each group.In addition to the blank group,the remaining groups of mice were given a 3.5% DSS solution for 7 days to create an acute phase model of UC mice.After successful modeling,the blank group was given free access to mineral water,and the remaining groups were given intragastric administration of normal saline,mesalazine,and low-Ding’s Herb Oral agent Prescription and high-Ding’s Herb Oral agent Prescription for 14 days to ensure experimental results.The general state of the mice was observed during this period.At the end of the 14 th day,all mice were sacrificed and the intestinal mucosal morphology was observed to evaluate the histological score of the colon mucosa.Western-Blot method was used to detect the expression of TNF-α,IL-6 and IL-17 in colon tissue of mice.The mechanism of Ding’s Herb Oral agent Prescription in the treatment of intestinal inflammation was verified.Results: 1.A total of 175 potential active ingredients were screened using the ADME/TOX virtual computing system.Thirteen of them did not find corresponding targets and constructed a component-target interaction network.The potential targets of Ding’s Herb Oral agent Prescription and the related targets of known ulcerative colitis were used as PPIs respectively.A related effect network was constructed and network analysis was conducted.The results showed that Ding’s Herb Oral agent Prescription was used to treat ulcerative colitis.The potential targets are closely related to IL-6,IL-17 and TNF-α protein and related signaling pathways.2 After the model was built,the mice were apathetic,lost weight,and had loose stools with mucus and bloody stools.Compared with the blank group,the DAI score increased(P<0.05).After treatment,the symptoms of mice in the mesalamine group and the Ding’s Herb Oral agent Prescription group improved significantly,and the DAI score was lower than that in the model group(P<0.05).In the low dose group of Ding’s Herb Oral agent Prescription,the treatment status was relatively poor compared with the mesalazine group and the high dose group of Ding’s Herb Oral agent Prescription,but it was superior to the model group.3.The colon mucosa of mice in each group was observed with naked eyes.Incomplete injury was observed in the model group,with obvious edema,congestion,and ulceration.The gross score was higher than that of the blank group(P<0.05).Ding’s Herb Oral agent Prescription group and Mesalazine group recovered after mucosal injury.Congestion,edema,and mild erosion were observed.There was no significant ulcer formation.The overall score was lower compared with the model group(P<0.05).4.Serving the colonic mucous membrane of mice in each group by microscope,it can be seen that the structure of the mucous membrane of colon mucosa in the model group is destructive,the arrangement is sparse,the inflammatory cells are infiltrated in a large amount,and the congestion and edema are more serious;No obvious ulcers were found in the mucosa of the Qin group,and inflammatory cell infiltration was observed.5 Compared with the blank group,the expression of TNF-α,IL-6,and IL-17 in the model group increased(P<0.01).Compared with the model group,the mesalamine group and the Ding’s Herb Oral agent Prescription High-dose group can significantly reduce the expression of TNF-α and IL-6(P<0.01),Ding’s Herb Oral agent Prescription low-dose group can reduce the expression of TNF-α(P<0.05);Compared with the model group,The high dose of Ding’s Herb Oral agent Prescription Group had the best effect in reducing the expression of IL-17(P<0.01).The Ding’s Herb Oral agent Prescription Low Dosage Group and Mesalamine Group had a good effect in reducing the IL-17 expression level.(P<0.05).Conclusion: 1.The mechanism of Ding’s Herb Oral agent Prescription in the treatment of UC may be that the multidrugs in Ding’s Herb Oral agent Prescription act on their targets and eventually reduce serum levels through the synergistic integration between the components and targets.The expression levels of inflammatory cytokines such as TNF-α,IL-6 and IL-17 play a role in the treatment of intestinal inflammation.2.Ding’s Herb Oral agent Prescription has a certain therapeutic effect on DSS-induced UC,can effectively relieve mice’s stool,bloody stool and weight loss,reduce inflammation of intestinal mucosal tissue,reduce DAI score and general score Improve pathological performance.Ding’s Herb Oral agent Prescription can reduce the inflammatory lesions of the intestine of UC model mice by down-regulating the expression levels of TNF-α,IL-6 and IL-17.