Glycyrrhizin suppresses oxidative stress injury in ulcerative colitis through Nrf2/HO-1 signaling pathway
Objective To investigate the effect of glycyrrhizin(GL)on oxidative stress in ulcerative colitis(UC)and its relation with nuclear factor erythroid-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods HT-29 cells were randomly divided into normal group,model group and low,medium and high GL concentration group.The oxidative stress model was induced in HT-29 cells by adding 0.8 mmol/L H2O2 in culture media,and the model cells were treated with 0.5,1.0,and 2.0 mmol/L concentration of GL for 24 h.The cell viability was detected by cell counting kit-8 method,the level of reactive oxygen species(ROS)was detected,and the protein expressions of HO-1,Kelch-like ECH-associated protein 1(Keap1),and Nrf2 were detected by Western blot.Twenty-four SD rats were divided into normal,model and GL intervention groups,with 8 rats in each group.The UC was induced by adding 5%dextran sulfate sodium salt in drinking water in model and GL intervention groups.The disease activity index(DAI)and tissue damage index(TDI)of rats were observed;rats were sacrificed at the end of the experiment,the length of colon was measured,and the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in colon tissues were detected;and the expressions of HO-1,Keap1 and Nrf2 in colon tissues were detected by Western blot.Results Compared with the model cell group,the cell survival rate was increased in the low,medium and high GL concentration groups(all P<0.05),the intracellular ROS level was decreased(P<0.05),the expression of HO-1 and Nrf2 was increased in medium and high GL concentration groups(all P<0.05);while the expression of Keap1 in the medium and high GL concentration groups decreased(both P<0.05).Compared with the model rats,DAI and TDI decreased(both P<0.05),colon length was longer(P<0.05),SOD level in colon tissue increased(P<0.05),MDA level decreased(P<0.05),Nrf2 and HO-1 expression significantly increased(both P<0.05),and Keap1 protein expression decreased in the GL intervention rats(P<0.05).Conclusion GL may suppress oxidative stress-induced injury by modulating the Nrf2/HO-1 signaling pathway,to exert therapeutic effects on ulcerative colitis.