Based on FXR/TGR5(farnesoid X receptor/ G protein-coupled bile acid receptor 5)pathway to explore the therapeutic effect and mechanism of action of total alkaloids from Sophora alopecuroides on 3.5% dextran sodium sulfate induced ulcerative colitis model in mice.Sixty healthy male BALB/c mice were divided into blank control group (Con),dextran sodium sulfate model group(DSS),sulfasalazine positive control group (SASP) and total alkaloids from S. alopecuroides treatment group(TASA).BALB/c mice were given 3.5%DSS water for continuous free drinking for 7 days to establish the mouse model of acute UC.During the modeling,S. alopecuroides extract(75 mg/kg) was given daily for treatment,and sulfasalazine (450 mg/kg) was used as the positive control drug.Clinical symptoms of mice in each group were scored by DAI during the experiment.Day eight,the pathological sections of colon were observed by HE staining,glycogen PAS staining and Alcian blue staining were used to observe the expression of goblet cells in colon tissue.The expressions of IL-10,IL-23,IL-1β and IL-17 in serum and colon tissue homogenate supernatant were detected by ELISA.The expressions of FXR,TGR5 and CYP7A1 in liver and colon tissues of mice were detected by Western blot. The results showed that after total alkaloids from S. alopecuroides extract treatment,the DAI,histopathological damage of colon and the length of colon were significantly improvement(P<0.01),the number of goblet cells in colon tissue was significantly increased (P<0.01),anti-inflammatory factor IL-10 was significantly increased (P<0.01),pro-inflammatory factors IL-23,IL-17 and IL-1β were significantly decreased (P<0.01),serum bile acid content was significantly increased (P<0.01),FXR,TGR5 and CYP7A1 in colon and liver were up-regulated.Results showed that the total alkaloids from S. alopecuroides had a certain therapeutic effect on DSS inducing UC in mice.It inhibited the development of colitis mainly by inhibiting the related inflammatory factors,and up-regulating the expression levels of related proteins of FXR/TGR5signaling pathway.