【Animal modeling】-Effect of curcumin on Keap1/ARE signaling pathway and bile acid enterohepatic circulation in liver cancer model mice

  Objective To investigate the effect of curcumin on cytoplasmic protein chaperone (Keap1)/antioxidant response element (ARE) signaling pathway and bile acid enterohepatic circulation in liver cancer model mice.

  Methods C57BL/6 mice were randomly divided into control group, model group, curcumin low-dose (10μg/g) group, curcumin medium-dose (20μg/g) group, curcumin high-dose group (30μg/g), cisplatin (10 μg/g) group, 12 in each group, except the control group, the other groups were induced to establish a liver cancer model by intragastric administration of diethylnitrosamine. After grouping, hematoxylin-eosin (HE) staining was used to detect the The pathological morphology of the liver tissue of the mice in the group; the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB) and total bile acid (TBA) in the serum of the mice were measured; enzyme-linked immunosorbent assay (ELISA) experiment Serum levels of interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) were detected in rats; Keap1/ARE in liver tissue was detected by real-time quantitative PCR (qRT-PCR) and Western blotting The expression of pathway-related protein Keap1 and nuclear transcription factor-related factor 2 (Nrf2).

  Results Compared with the control group, the liver tissue of the model group had pathological damage such as canceration, the serum ALT, AST, TB, TBA, IL-6 and TGF-β1 levels, and the Keap1 mRNA and protein levels in the liver tissue were significantly increased (P<0 . 05), the mRNA and protein levels of Nrf2 were significantly decreased (P<0.05); compared with the model group, the pathological damage of the liver tissue of the mice in the curcumin low, medium and high dose groups and the cisplatin group was alleviated, and the serum ALT, AST, TB, The levels of TBA, IL-6 and TGF-β1, and the mRNA and protein levels of Keap1 in liver tissue decreased, while the levels of Nrf2 mRNA and protein increased, and each index changed in a gradient with the increase of curcumin dose (P<0.05). there="" was="" no="" significant="" difference="" in="" each="" index="" between="" the="" dose="" group="" and="" cisplatin="" p="">0.05).

  Conclusion Curcumin can alleviate liver injury and improve enterohepatic circulation of bile acids in mice with hepatocellular carcinoma, which may be achieved by down-regulating Keap1 expression and activating downstream ARE signaling.