Exploration on the mechanism of hesperidin in the treatment of ulcerative colitis based on network pharmacology and experimental verification
Objective To explore the mechanism of hesperidin in treating ulcerative colitis(UC)by using network pharmacology and animal experiment.Methods The related targets of hesperidin were screened by SwissTargetPrediction database.The target information corresponding to ulcerative colitis was found by using OMIM and GeneCards databases.Using STRING online database,the drug targets and disease targets were matched,and then the intersection targets were selected to construct a protein-protein interaction(PPI)network model.GO enrichment and KEGG pathway enrichment of intersection targets were analyzed by R language.Fifty SPF ICR mice were randomly divided into control group,model group,mesalazine group,low-dose group of hesperidin(200 mg/kg),and high-dose group of hesperidin(400 mg/kg),10 mice/group.Using DSS to induce mice to become UC model,the mice were killed on the seventh day of modeling and the samples were take,the disease activity index(DAI)of mice in each group was scored,and the weight change and colon length difference of mice in each group were compared.HE staining was used to observe the histopathological changes of colon of mice in each group.The levels of interleukin 6(IL-6)and tumor necrosis factor-α(TNF-α)in serum of mice were detected by ELISA.The content of short-chain fatty acids(SCFAs)in intestinal contents of mice was detected by gas mass spectrometry-chromatography.Results The results of network pharmacology showed that there were 15 related targets of hesperidin in the treatment of UC.Through PPI network model,it was concluded that ESRI,ALB and ACE might be the main targets of hesperidin in the treatment of UC,and the core signal pathway of hesperidin in the treatment of UC was obtained through GO and KEGG enrichment analysis.The results of animal experiments showed that DAI score of UC mouse model was decreased,weight loss was alleviated,colon length was increased,the differences were statistically significant(F=4.725,11.990,109.400;all P<0.05).Compare with that model group,serum IL-6,TNF-α levels of UC mice after intervention of hesperidin were decreased(F=167.700,154.800;all P<0.05);the contents of acetic acid,butyric acid,propionic acid,caproic acid,valeric acid,isobutyric acid and isovaleric acid all increased in different degrees,and the contents of butyric acid and valeric acid increased significantly(F=3.440,8.374;all P<0.05).Conclusion Hesperidin could improve UC symptoms by regulating the main targets and increasing the amount of SCFAs in intestinal contents of mice.