Abstract: 【Objective】 Based on network pharmacology and molecular docking,the active ingredients and targets of Euphorbiae humifusae herba in the prevention and treatment of ulcerative colitis (UC) were analyzed,and its potential mechanism was explored to protect the intestinal tract of animals.【Method】 The active ingredients and corresponding drug targets of Euphorbiae humifusae herba were obtained by TCMSP database.Disease targets were obtained from GeneCards,DisGeNET,TTD,PharmGKB and DrugBank databases.Potential targets were obtained by intersecting drug targets and disease targets,and the protein-protein interaction (PPI) analysis and GO function and KEGG pathway enrichment analysis of potential targets were performed by STRING and DAVID databases,respectively.AutoDock 1.5.7 software was used for molecular docking verification,and PyMOL software was used to visualize the docking results.Sodium dextran sulfate (DSS)-induced UC model was established in 30 BALB/c mice in vivo.Control group,model group,Euphorbiae humifusae herba low (5 mg/mL),high dose group (15 mg/mL) and mesalazine group (52 mg/mL) were set up.Except for control group,mice in the other groups were free to drink 3% DSS to induce UC model for 7 d. Mice in the drug treatment group was intragastrically administered with 0.2 mL of the corresponding dose once a day.Mice in control and model groups were intragastrically administered with the same volume of sterile normal saline for 7 d.The changes of body weight,disease activity index (DAI) score and colon length were measured,and the contents of tumor necrosis factor-α(TNF-α),interleukin-6 (IL6) and IL10 were detected.【Result】 The main active ingredients of Euphorbiae humifusae herba were kaempferol,4’-5-dihydroxyflavone and ellagic acid,with 256 corresponding drug targets,4 265 disease targets,128 potential targets and 7 core targets.GO functional enrichment involved response to reactive oxygen species,response to oxidative stress,inflammatory response,membrane raft,cave,kinase regulator activity,etc.KEGG signaling pathway involved PI3K-Akt and TNF signaling pathways,and so on.Molecular bonding results showed that kaempferol and peroxisome proliferator-activated receptor γ (PPARG),4’,5-dihydroxyflavone and PPARG,ellagic acid and serine/threonine protein kinase 1 (AKT1),ellagic acid and IL6 had strong binding potential.In vivo experiments showed that compared with control group,mice in model group had severe weight loss,severe watery bloody stools,and an extremely significant increase in DAI score(P＜0.01).A large number of inflammatory cell infiltrations were found in the mucosa and submucosa of the colon tissue,and even small ulcers appeared,indicating that the mouse UC model was successful.Compared with model group,the infiltration of inflammatory cells in the colonic mucosa of each administration group were reduced,the DAI score was extremely significantly reduced (P＜0.01),the colonic contracture was improved,the contents of TNF-α and IL6 were significantly reduced (P＜0.05),the content of IL10 was significantly increased (P＜0.05),and the inflammation was inhibited.【Conclusion】 The main active ingredients such as kaempferol,4’-5-dihydroxyflavone and ellagic acid in Euphorbiae humifusae herba might participate in inflammation-related signaling pathways and biological functions by acting on core targets such as AKT1,PPARG and IL6,inhibited inflammation and reduced intestinal damage,thus exerting the effect of preventing and treating UC.

Key words: Euphorbiae humifusae herba; ulcerative colitis; network pharmacology; molecular docking; mechanism