This study aims to explore the protective effects and molecular mechanisms of probiotic fermented Astragali Radix (F-As) and non-fermented Astragali Radix (As) on the oxidative damage in lipopolysaccharide (LPS)-induced normal human colon epithelial cell NCM-460.The working concentrations of LPS,As and F-As were determined by MTT assay.The changes of oxidative stress-related indexes and antioxidant-related genes at transcription level and protein level in LPS group,As + LPS group and F-As + LPS group were detected and compared respectively.Compared with the control group,reactive oxygen species (ROS) and malondialdehyde (MDA) were significantly increased (P<0.01) after treatment of LPS,while cell viability,glutathione (GSH),superoxide dismutase (SOD),total antioxidant capacity (T-AOC) and antioxidant-related genes were decreased (P<0.01).Compared with the LPS group,As + LPS group and F-As + LPS group,the content of ROS and MDA were obviously decreased (P<0.01),whereas the content of GSH,SOD,T-AOC and antioxidant-related genes were increased (P<0.01),compared with the LPS group.However,compared with As group,F-As showed a more significant effect on enhancing these bio-indicators as mentioned above (P<0.05).The results suggest that both As and F-As can remove excessive ROS and MDA in cells by activating the expression of antioxidant genes,thus playing a protective role in LPS-induced oxidative damage of cells,and F-As is superior to As.