Bilobalide Enhances AMPK Activity to Improve Liver Injury and Metabolic Disorders in STZ-Induced Diabetes in Immature Rats via Regulating HMGB1/TLR4/NF-κB Signaling Pathway

Abstract

This study was aimed at examining the effect and underlying mechanisms of bilobalide (BB) on hepatic injury in streptozotocin- (STZ-) induced diabetes mellitus (DM) in immature rats. Immature rats (one day old) were randomly divided into five groups: group I, control nondiabetic rats; group II, STZ-induced, untreated diabetic rats; groups III/IV/V, STZ-induced and BB-treated diabetic rats, which were intraperitoneally injected with BB (2.5 mg/kg, 5 mg/kg, or 10 mg/kg) after 3 days followed by STZ treatment. We observed that BB improved the histopathological changes and maintained normal glucose metabolism, blood lipid, and liver function indicators, such as fasting blood glucose, obesity index, HbA1c, HOMA-IR, fast serum insulin, adiponectin, total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), aspartate transaminase (AST), and alanine transaminase (ALT) in STZ-induced DM in immature rats by a biochemical analyzer or ELISA. Meanwhile, Western blot analysis showed that in STZ-induced DM immature rats, BB decreased the expression of apoptosis-related proteins Bax, cleaved caspase-3, and cleaved caspase-9 while enhancing the Bcl-2 expression; BB downregulated the expression of ACC related to fat anabolism, while upregulating the expression of CPT-1 related to fat catabolism. Strikingly, treatment with BB significantly increased the expression of AMPKα1 as well as inhibited HMGB1, TLR4, and p-P65 expression in hepatic tissues of immature DM rats. AMPK inhibitor (compound C, CC) cotreated with BB undermined the protective effect of BB on the liver injury. The results of the present study suggested BB may have a significant role in alleviating liver damage in the STZ-induced immature DM rats.