1-Deoxynojirimycin Ameliorates Diabetic Liver Injury by Regulating AMPK/SIRT1 and Oxidative Stress in db/db Mice.

Abstract

Background: Patients with diabetic liver injury are in the dilemma of lowering glucose and protecting liver function. This study aimed to uncover the protective effect and mechanism of 1-deoxynojirimycin (1-DNJ), an alpha-glucosidase inhibitor, against diabetic liver injury.

Methods: The db/db mice were gavaged with 25 mg/kg, 50 mg/kg, and 100 mg/kg of 1-DNJ for 8 weeks. At the end of the administration, the serum and liver were isolated for further detection. The biochemical indices including TC, TG, LDL-C, AST, ALT, and TBiL were detected in serum. The livers were further analyzed with H&E, oil red, and Masson staining, and the amount of ROS in the liver was detected with probe dihydroethidium. Western blot was used to analyze the levels of proteins involved in fibrosis, oxidative stress, and AMPK/SIRT1 signaling pathway in the liver.

Results: 1-DNJ administration reduced body weight, liver coefficient, and TC, TG, LDL-C, AST, ALT, and TBiL in db/db mice. H&E and oil red staining showed that 1-DNJ ameliorated hepatocellular ballooning degeneration and lipid deposition in the liver. Moreover, 1-DNJ reduced the hepatic collagen fiber deposition and the protein expression of α-SMA and Collagen I. Further assays revealed that 1-DNJ treatment reduced the ROS level, up-regulated the proteins expression of SOD2, HO-1, NQO-1, p-AMPK/AMPK, p-ACC/ACC, and SIRT1 proteins, and down-regulated the expression of SREBP-1 and SCD-1 proteins in the liver.

Conclusion: 1-DNJ improves liver function, lipid deposition, and fibrosis of diabetic liver injury in db/db mice by regulating the AMPK/SIRT1 pathway to improve glucose-lipid metabolism and oxidative stress.